ISSN:0144-557X    

DOI:10.1039/AP99128FX021

出版商:RSC    

年代:1991

数据来源: RSC

摘要:

ANPRDI 28(6) 169-208 (1991) Proceedings of the Analytical Division of The Royal Society of Chemistry 169 Reports of Meetings 169 1991 Review of Analytical Division Subject Groups 174 1991 Schools Analyst Competition 174 Presentation of AnalaR Medal 175 Analytical Viewpoint 175 'Comparison of Coprecipitation and Chelating Ion Exchange for the Preconcentration of Selected Heavy Metals From Sea-water' by Michael N. Quigley and Frederick Vernon 177 SUMMARIES OF PAPERS 177 Biomedical and Pharmaceutical Chemistry 177 178 179 181 183 185 186 'Implications of Regulatory Requirements for Bioanalytical Techniques and Resources' by Colin W. Vose 'Liquid-Liquid and Liquid-Solid Phase Extraction as Applied to the Determination of Drugs in Biological Samples' by Robin Whelpton 'Use of Mass Spectrometry in Pharmaceutical Analysis' by Alison E.Ashcroft 'High-resolution Nuclear Magnetic Resonance Spectroscopy of Biofluids and Applications in Drug Metabolism' by Jeremy R. Everett 'Strategic Applications of Proton Nuclear Magnetic Resonance Spectroscopy in Clinical Biochemistry and Analytical Toxicology' by J. K. Nicholson and I. D. Wilson 'Enantiospecific Bioanalysis' by Andrew J. Hutt 'Supercritical Fluid Chromatography of Polar Compounds' by E. David Morgan, Huiping Huang and Ian D. Wilson 189 Teaching of Modern Analytical Chemistry-Fitting the Skills 1 89 189 190 191 'The Aims of Teaching Analytical Science in Higher Education' by F. W. Fifield 'Computer-assisted Learning of Analytical Chemistry' by John Boother 'Analytical Short Courses for Industrial Needs' by Roger M.Smith 'Continuing Professional Development for Analytical Chemists' by Norma Chadwick 193 Research and Development Topics in Analytical Chemistry 193 194 197 'Applications of a Slotted Tube Atom Trap and Flame Atomic Absorption Spectrometry: Determination of Antimony in Copper-based Alloys After Hydride Generation' by Michael Harriott, D. Thorburn Burns and Narong Chimpalee 'Determination of Total Tin in Acid Digests of Seaweed and Sediments Using Hydride Generation and Quartz-tube Electrothermal Atomization' by Michael Harriott, D. Thorburn Burns and Colin Donaghy 'Ternary Complex Formation Between Alizarin Fluorine Blue, Lanthanoid Ions and Ethylenediaminetetraacetic Acid Type Chelating Ligands' by Brian Bingham, Rose Boyle, Marie M. Ferris and M. A. Leonard 202 Equipment News 204 IFST President 205 Conferences and Meetings 206 Courses 207 Publications Received 208 Analytical Division Diary Typeset and printed by Black Bear Press Limited, Cambridge, England June 1991 Analytical Proceedings CONTENTS

ISSN:0144-557X    

DOI:10.1039/AP99128BX023

出版商:RSC    

年代:1991

数据来源: RSC

摘要:

ANALYTICAL PROCEEDINGS, JUNE 1991. VOL 28 169 I991 Review of Analytical Division Subject Groups The annual review of the remits and activities of three of the Subject Groups is now an established event in the calendar of the Group Liaison and Policy Commit- tee. Reports of the two earlier reviews have been published in this journal.1.’ The third review was conducted at the January meeting of the GLPC. It dealt with the activities of the Electroana- lytical, Particle Characterization and Radiochemical Methods Groups. The Groups presented reports which were discussed in depth by the GLPC. It was generally agreed that the remits of these Groups are satisfactory and that they are being managed well. No changes to roles or act i v i ti es we re con si de re d desi ra b 1 e .Summaries of the presentations made by the Groups are given below. References 1 Watson. C. A , . Atiul. l’roc., IY8Y. 26. 2 Newman. E. J . , And. Proc.. 1990. 27, E. J . NEWMAN 132. lY7. Electroanalytical Group The Group’s foundations were laid in 1950 with the formation of the Polaro- graphic Society, which played an active and major role in the promotion of electroanalytical chemistry in the UK into the next decade, organizing national and international meetings and publishing the Joiirnul of’ thc Polurogruphic Society. R y the mid-l960s, the field of analytical electrochemistry had broadened and the Society for Electrochemistry (now the Electrochemistry Group, Faraday Div- ision) has been formed. I t was considered that the interests of electroanalytical chemistry would be best served by the Polarographic Society being more closely associated with the wider field of analy- tical chemistry.This was achieved in 1969 by its amalgamation into the (then) Society for Analytical Chemistry as the Electroanalytical Group. Objectives The inaugural remit of the Group was: ‘to encourage, assist and cxtend the study of electroanalytical methods’, and it remains so today. These objectives are met by: sponsor- ing lectures and conferences, either alone or in association with other relevant bodies; providing assistance to students to attend selected meetings; and triannual circulation to the membership of the ‘Electrochemistry Newsletter’. a joint publication with the Electrochemistry Group (Faraday Division) and the Elec- trochemical Technology Group (SCI).Committee Membership Conscious effort is made to maintain a representative balance, both throughout the UK and between academia and industry. ‘There is cross-committee rep- resentation of one member with the Elec- trochemistry Group Committee. The committee members are active on other related bodies, both within and outside the RSC. The President of the Division, Professor J. D. R. Thomas, is a former Group Chairman. He has also held appointments as Division Honorary Secretary, Council Member, Chairman of the Analytical Editorial Board and has been Chairman of the Western Region and the (former) Education and Training Group. Dr. A. G. Fogg, Chairman of the Analytical Editorial Board, is a former Group Chairman, and has also held appointments as Division Vice-chairman and Council Member, has been active on the Midlands Region Committee. The Group’s Honorary Treasurer, Dr.B. J. Birch, is a former Council Member, is the Division’s Member on the Industrial Div- ision Council, a Committee Member of the Institute of Measurement and Control and sits on the DTI Link Molecular Sensors Committee. Other members are committee mem- bers of the Electrochemistry, Industrial and Chemometrics Groups and are on BS, IUPAC, other national and interna- tional committees, and the Standing Committee of Analysts. Awards presented to Committee Mem- bers of the last three years include: The RSC/Pye Unicam Electroanalytical Chemistry Award, J . D. R. Thomas 1981, A. K. Covington 1986, A. G. Fogg 1989; The R. A. Robinson Memorial Lecture- ship, A. K.Covington 1983; The Ronald Belcher Memorial Lectureship, J. M. Slater 1988; The SAC Silver Medal, D. Midgley 1980; and The University of Bologna 900th Anniversary Sigilliim Magnum, A . K. Covington 1987. Meetings These are listed in the Honorary Secre- tary’s reports in Appendix 1, and the170 ANALYTICAL PROCEEDINGS, JUNE 1991. VOL 28 programmes detailed in Appendix 2. In the three-year period the major meetings sponsored or co-sponsored have been the ‘39th Annual Meeting of the International Society of Electrochemistry’ at Strathclyde University in September, 1988, the ‘Biennial International Sym- posium on Electroanalysis’ at Lough- borough in April, 1989, an international meeting on ‘Electroanalysis and Chemometrics of Speciation of Natural Waters’ at Liverpool in July, 1990, and in December, 1990, the ‘Heyrovsky Cen- tenary Meeting’ in London.Group policy is generally to arrange joint meetings, providing an interface with other bodies and, when appropriate, with the local region. When practical, such meetings may be of the ‘workshop’ variety and provide the opportunity to arrange an associated exhibition of com- mercial instrumentation. Whilst recognizing the clear, separate roles of the two Groups, a close relation- ship has been established with the Elec- trochemistry Group, with which there is substantial cross-membership. The general policy of the two Groups is to co-sponsor meetings and have a joint approach on such matters as student support. Future Meetings In the immediate year ahead, a meeting will be held on ‘Microelectrodes for Analysis’, at which the principal eontribu- tor on this topic of current interest will be Professor A.M. Bond (La Trobe Univer- sity). The major event of the year is the RSC Sesquicentenary Meeting in April, at which the Group is co-sponsoring, with the Electrochemistry Group, the meeting on ‘New Electrochemical Sensors’ on behalf of the Analytical and Faraday Divisions. This meeting incorporates the Group’s next Biennial Symposium. The following Biennial Symposium will be held in April, 1993. Future Policy The future policy of the Group will take account of the results of the ‘RSC Work- ing Party on the Future of Analytical Chemistry’, and will respond to the changing needs of academia and industry. The Group has recently become asso- ciated with the European Community ‘Initiative on Sensors’, and obviously closer European liaison will develop.Financial Situation The Group is on a sound financial basis. APPENDIX I Honorary Secretary’s Report 198911990 Seven meetings were held during the period from August, 1989, to December, 1990. 1. December 15th, 1989. St. Thomas’s 2. 3. 4. 5. 6. 7. Hospital, London: ‘In-Vivo Measure- ments’. Joint meeting with the United Medical and Dental Schools’ Group, the South East Region and the Asso- ciation of Clinical Biochemists. Atten- dance 25. February 6th’ 1990. Polytechnic, Wol- verhampton: ‘Software for Electro- analytical Chemistry’. Joint meeting with the Chemometrics Group. Atten- dance 60. March 14th, 1990. Imperial College, London: ‘Graduate Students’ Meet- ing’.Joint Meeting with the Electro- chemistry Group (Faraday Division) and the Electrochemical Technology Group (Society of Chemical Industry). Attendance 50. March 28th, 1990. Kodak Ltd., Har- row: AGM and ‘Process Control and Monitoring Using Electrochemical Techniques’. Joint meeting with the Midlands and South East Regions and the Institute of Measurement and Con- trol. Attendance 50. May 30th, 1990. University, Edin- burgh: ‘Butler Lecture and Graduate Students’ Meeting’. Joint Meeting with the University Chemistry Dcpart- ment, the Electrochemistry Group (Faraday Division) and the Electro- chemical Technology Group (SCI). Attendance 50. July 9th-11th. 1990. University, Liver- pool: ‘Electroanalysis and Chemo- metrics of Speciation of Natural Waters’.Joint meetingwith theChemo- metrics Group. Attendance 60. December 12th, 1990. University Col- lege, London: AGM and, ‘Heyrovsky Centenary Meeting’. Joint meeting with the Historical Group and the Electrochemistry Group (Faraday Division) in association with Univer- sity College, London. The 1991 AGM had been brought for- ward to December 1990 due to the early holding of the 1991 Division AGM. Current Group membership was 373, a decrease of 21 on the previous year. APPENDIX I1 Meetings Programmes 1 988 May 4th- Hayes: ‘Electrochemical Sensors’. ‘A Flow-through ISFET’ J . E. A. Shaw and A. Sibbald (Thorn-EMI). ‘Composite Gate ISFET Devices’ J . E. A. Shaw and P. D. Whalley (Thorn-EMI). ‘Membranes for ISFETS’ J. M. Slater (U W I ST).‘Enzyme-modified FETS’ G. K. Chandler, M. J. Eddowes and J . R. Dodgson (Thorn-EMI). ‘Change of Image-Electrochemistry on Film’ E. C. Weller (Kodak). ‘Iridium Oxide pH Sensors’ M. L Hitch- man (Strathclyde University). ‘Immunosensors-Fundamental Chem- ical Limitations’ M. J. Eddowes (Thorn- EMI). ‘Clinical and Other Applications of ISFETS’ A. K. Covington (University , Newcastle upon Tyne). ‘Application of Surface Plasmon Res- onance (SPR) to Biosensors‘ J. C. Irlam, M. J. Eddowes and P. B. Daniels (Thorn- EMI). June 10th- London: ‘Graduate Students’ Meeting’. December 9th- London: ‘Electrochemical Determination of Alcohol’. ‘Introduction and Overview of Fuel Cells and their Application to Alcohol Deter- mination’ W. J. Criddle (University of Wales, Cardiff). ‘Electrochemical Determination of Ethanol in Alcoholic Beverages’ K.W. Parry (Kent Industrial Measurements). ‘Development of a Sensor for Ethanol’ V. Sim (Laboratory of the Government Chemist). ‘Direct Potentiometry for Ethanol in Ethanol-Water Mixtures and in Drinks Using the lsoconcentration ‘Technique’ G. J . Kakabadse (UMIST). 1989 April 11/14th- Loughborough: ‘International Sym- posium on Electroanalysis in Biomedical, Environmental and Industrial Sciences’. Plenary Lectures: ‘From Frogs Legs to Chips-200 years of Electroanalysis’ A. K . Covington (Uni- versity, Newcastle upon Tyne). ‘Some Aspects of Flow Electroanalysis’ K. Stulik (Charles University, Prague). ‘HPLC-ED in Biochemical Research’ D. Perrett (St. Rartholomew’s Hospital, London). ‘Arrays of Electrodes for Multicom- ponent Analysis’ W.E. van der Linden (University, Twente). ‘Cathodic Stripping Voltammetry of Trace Elements in Sea Water’ C. M. G. van den Berg (University, Liverpool). ‘Applied Polarography and Voltammetry in Industry’ P. Bersier (Ciba-Geigy, Bask). ‘A t-Depth Vol tammetry Measurements in Lakes: Why and How?’ J. Buffle (Univcrsity, Geneva). ‘New Electrochemical Approaches to Analysis of Electrophoresis Gels’ M. L. Hitchman (Strathclyde University). ‘Pol yet hers as Po te n tiome tric Sensors’ J . D. R. Thomas (University, Cardiff). May 31~t- Edinburgh: ‘Butler Lecture and Graduate Students’ Meeting’. ‘New Directions in Semiconductor Elec- trochemistry’ L. M. Peter (University, Southampton).ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 171 ‘Electrochemical Gas Sensors’ A.McIntyre (Strathclyde University). ’Artificial Gills-a New Approach’ S. Turner (Heriot-Watt University). ‘Spectroelectrochemical Study of Bi- metal Complexes’ R. Sorbie (University, Edinburgh). ‘Analytical Determination of CrV[ in Cor- rosion Studies’ N . G. Smart (Glasgow College of Technology). ‘Ion Motion in Protective Polymer Coat- ing’ B. Johnson (University, Newcastle upon Tyne). ‘Charge Transport Processes in Redox Polymer Modified Electrodes’ H. Fay (Trinity College, Dublin). ‘Mass Transport in Cells Based o n Poly- mer Electrodes’ M. Hardgrave (Univer- sity, St. Andrews). December 1Sth- London: ‘In-siiw Electroanalysis’. 25 Years of /n-\li,w Monitoring’ D. Band (St. Thomas’s Hospital, London). ‘Microdialysis as an In-vivo Sampling Technique’ A.Corin (Karolinska Insti- tute, Stockholm) and R. Newton (Biotech Instruments, Lu ton). ‘Implanted Electrodes for Monitoring Neurotransmitters’ M. Filenz (Univer- sity, Oxford). ‘The EC Concerted Action Programme on Chemical Sensors for In-viiw Monitor- ing’ A. Turner (Cranfield Institute of Technology). ‘Iri-11iiw Monitoring of Glucose’ G . Reach (Hotel Dieu, Paris). ‘pH Measurement in Myocardial Research Using ISFETS’ A. K. Coving- ton and E. Valdez (University, Newcastle upon Tyne). ‘Ion-selective Microelectrode Technol- ogy’ C. Fry (St. Thomas’s Hospital, Lon- don). I990 February 6th- Wolverhampton: ‘Software for Electro- a n a 1 y t i c a 1 C h e mist r y ‘ . ‘The Electronic-Electrochemical Inter- face’ T . E. Edmonds (University, Lough- borough).‘New Developments in Amperometric Techniques’ H. Girault (University, Edinburgh). ‘Automatic Optimization of Voltammet- ric Sensors and Systems’ P. Fielden (DIAS, UMIST). ‘Fitting Potentiometric Data’ L. Pettit (University, Leeds). ‘Computer-Associated Poten tiome tric Analysis’ J. R. Entwhistle and E. Liptrol (Fylde Scientific Ltd.). ‘Turning Software into Products’ J . Comer (Orion UK Ltd.). March 28th- Harrow: ‘Process Control and Monitoring using Electrochemical Techniques’. ‘Environmental Aspects of Electrochem- ical Process Control’ M. Comber (ICJ, Brixham). ‘Monitoring High-purity Water in Power Stations’ D. Midgley (CERL, Leather- head). ‘Electrochemical Measurement and Con- trol in Fermenters’ C. Kent (University, Birmingham). ‘Microelectrodes, Electroanalysis and Process Monitoring’ D.Craston (AEA, Harwell). ‘Process Control and Measurement’ P. Clark (ICI/UMIST). ‘On-line Titration in the Process Industry’ H. Pap (Applikon UK). ‘Active Electrochemistry in Process Measurement’ K. Dawes (Windsor Scien- tific). March 14th- London: ‘Graduate Students’ Meeting’. ‘Electrochemical Behaviour of Cu-Fe Sulphides’ F. Dean (Imperial College, London). ‘An Enzyme Electrode for Bile Acids’ G . Rao (Imperial College, London). ‘Electroreflectance and Electrochemistry’ R. Batchelor (University, Oxford). ‘The Mechanism of Some Photoelectro- chemical Reactions’ A. Fisher (Univer- sity, Oxford). ‘The Direct Electrochemistry of Protein- Protein Complexes’ L.-H. Guo (Univer- sity, Oxford). ‘Ion Transport in Polypyrrole and Re- lated Conducting Polymers’ A.Milling- ton (University, Salford). ‘Photocurrents from Pt in Aqueous Elec- trolytes’ A. J. Rudge (University, South- ampton). ‘SCALPEM-Scanning Laser Photoelec- trochemical Microscopy’ A. R. J. Kucer- nak (AEA, Harwell). ‘Polypyridine: a Metal-Chelating, Con- ducting Polymer?’ V. Eastwick-Salehi (University of Warwick). ‘Electrowinning of Zn from Alkaline Electrolytes’ J . St. Pierre (University, Exe ter). May 30th- Edinburgh: ‘Butler Lecture’ and ‘Gradu- ate Students’ Meeting’. ‘Localized Corrosion of Stainless Steel’ D. Williams (AEA, Harwell). ‘New Mediators for Amperometric Biosensors’ B. Moore (Strathclyde Uni- versity). ‘A1 and Alloy Substrates of the Recharge- able Li Electrode’ R. Ram (University, Newcastle upon Tyne).‘Amperometric Chemical Sensors Based on Conducting Polymer’ W. Breen (Trin- ity College, Dublin). ‘Different Mass Transfers to a Liquid- Liquid Interface’ A. Stewart (University, Aberdeen). ‘Electrochromism in Polymer Electrolyte Devices’ P. Monk (University, Aber- deen). ‘Polymer Electrolyte-Intercalation Elec- trode Interfaces’ Eileen McGregor (Heriot-Watt University). ‘Analytical Investigations Using Micro- electrodes and Impedance Spectroscopy’ A. MacNaughton (Glasgow College of Technology). July 9th- Liverpool : ‘Electroanal ysis and Chemometrics of Speciation of Natural Waters’. ‘Stripping Voltammetry of Metal Com- plexes with Synthetic and Natural Poly- electrolytic Ligands’ H. P. Van Leeuwen (University , Wageningen) . ‘Development of Lichen-Modified Car- bon-Paste Electrodes for Bioselective Accumulation of Heavy Metal Ions’ M.R. Smyth (City University, Dublin). ‘The Double Acidification ASV Tech- niques for Determining the Toxic Frac- tions of Cd, Pb and Cu in Waters’ M. T. Florence (CSIRO, NSW). ‘The Effect of the Detection Window on the Determination of Metal Complexa- tion in Sea-water’ C. M. G. van den Berg (University, Liverpool). ‘Determination of Cu Complexation Using a Combination of CSV and Com- puter Simulation’ J. Ravenscroft and M. Gardner (WRC). ‘Determination of Cr Speciation in Sea Water’ M. Boussemart (University, Liverpool). Voltammetry for In Situ Concentration and Speciation Measurements’ J . Buffle (University , Geneva). ‘Electrochemical Speciation Studies’ W. Davison (FBA, Ambleside).‘Metal Speciation and Toxicity’ G. Morri- son (University, Gothenburg). ‘Speciation of Zn in Oceanic Waters’ K. Bruland (University of California). ‘Pb Specification in the Antarctic Ocean’ G. Scarponi and G. Capadaglio (Univer- sity, Venice). ‘Interaction of Hydrophobic Organic Compounds with Adsorbed Lipid Layers’ A. Nelson (PML, Plymouth). ‘Investigations by HPLC with ICP and Electrochemical Detection of Organo- metallics in Marine Ecosystems’ A. Mazzucotelli (University, Genoa). December 12th- London: ’Heyrovsky Centenary Meet- ing’. ‘The Life and Work of Jaroslav Hey- rovsky’ P. Zuman (Clarkson College, Potsdam, NY), ‘University College London in Hey- rovsky’s Time’ J. K. Roberts (Open University). ‘Early Industrial Applications of Polar- ography’ J. E .Page (formerly, Glaxo, Greenford). ‘Scope and Limitations of Advanced Vol- tammetric, Tensammetric and Hybrid Techniques in the Industrial Laboratory’ P. M. Bersier (Ciba-Geigy, Basle). ‘Polarography Today and Tomorrow’172 ANALY? Janet G. Osteryoung (SUNY, Buffalo, NY). Particle Characterization Group The role of the Group is to provide a focus for discussion of those aspects of ana- lytical methodology which are used to characterize particles in terms of their size, shape, surface area or porosity. The objectives are to promote and extend the knowledge, understanding, scope and application of particle charac- terization techniques to fundamental research, process control and quality assurance. These are achieved through lectures, colloquia, symposia and international conferences organized by the Group itself or in conjunction with another Group, region or other body consistent with the requirements of the Royal Society of Chemistry.The objectives of the Group are met by the presentation and publication of high quality papers concentrating on all aspects of particle characterization, by residential conferences and non-residen- tial meetings. The demonstration of equipment at the forefront of particle technology is encouraged at residential meetings and review meetings are held periodically to update people with current trends. Contacts are maintained with similar bodies in Europe, North America, Africa, Australasia and the Far East to ensure a truly international dissemination of up-to-date information. The Group Committee is representa- tive of the broad population of the Group.Its members come from industry, aca- demia, government bodies (MSE, MOD and UKAEA) and companies engaged in manufacturing and marketing instru- ments for particle characterization. A list of meetings sponsored in the past three years, and planned for the next two years, appears in Table 1 . The financial state of the group is extremely healthy. Radiochemical Methods Group Objectives The objectives of the Group are ‘to encourage, assist and extend the knowl- edge and study of radiochemical methods of analysis’. The radioactivity may be natural to the sample, introduced to the sample or form part of the detector system. Laboratory design, instrumenta- tion, safe handling, safety procedures, disposal and transport of radioactive sub- stances are also considered to lie within the range of the Group’s activities.While much emphasis is placed on recent deve- lopments in the fields of interest of established practitioners, the Group is very conscious of the need to assist and encourage those who are using radio- chemical techniques for the first time. In order to meet these objectives, the Group organizes a range of events. Each year there is a series of one and two day meetings and there is a biannual work- shop designed specifically for those new to techniques used in radiochemistry. In addition, there are organized meetings of an international nature. The Group regularly collaborates with AEA Technology, various Government Ministries, BNFL and Nuclear Electric on a Symposium entitled ‘Environmental Radiochemical Analysis’.International meetings in collaboration with overseas chemical societies are also held. CAL PROCEEDINGS, JUNE 1991, VOL 28 Every other year, the Group holds a ‘Young Researchers’ meeting at which a trophy and cash prize is given for the best presentation. The objective of this meet- ing is to improve communication skills amongst young scientists. The Group also encourages joint meetings between itself and Regions, and other Groups, within the Royal Society of Chemistry. Membership The Group is International in nature (15 countries are represented) and more than 10% of the membership is from overseas. The membership numbers have remained fairly constant during the past four years: 316 (1990), 307 (1989), 307 (1988) and 316 (1987).Composition of the Committee The membership of the Committee is composed of those working in industrial, government and academic establish- ments. Since the Group’s establishment, it has had little difficulty in attracting enthusiastic members to its Committee. Past Meetings A list of meetings held during the past 4 years is shown in Table 2. The subjects of these events reflect the wide-ranging interest shown in radiochemical methods and their applications. Future Programme and Policies The future programme is shown in Table 3. The Group will continue to promote the teaching and practice of radiochem- ical methods by organizing Workshops, Meetings, Symposia and Conferences. Committee members have recently dis- Table 1 Meetings sponsored by the Particle Characterization Group.1987-1992 Date Title 2/4/87 10/6/87 16/9/87 1/12/87 19-20/4/88 PSA 88 International Confcrencc 6/9/88 On-line particle characterization 2911 1/88 22/2/89 Measurement of man-made fibre5 14/3/89 Surface characterization of pharmaceuticals 8/6/89 Particle shape: Definition and measurcmcnt Electrical effects on fine particles in gases Particles in hot gases-sampling and sample preparation Particle size measurement-calibration and traceability AGM and Electrophoretic mobility and particlc characterization in liquid dispersed systems AGM and Use and abusc of particlc characterization 511 2/89 20/3/90 5/9/90 411 2/90 251319 1 1 61419 1 17-1 9/9/91 3/12/91 Spring, 1992 AGM and Young Author Award Characterization of agglomerates, granulates Particle sizing: an update AGM and Young Author Award: Solving the problems of sub-micrometre particle characterization Particle shape Particles today.hosted by Coulter Electronics PSA 9 1 lnternational Conference AGM and Young Author Award Characterization of clay particle sizdshape, joint with and compacts Clay Minerals Group of Mineralogical Society Venue Spons. org. Surrey PCG London PCG NPL PCG London PCG Surrcy Harwcll London London Bradford Lough borough London Aldermaston PCG PCG PCG PCG PCG PCGI PCG PCG Aero. Soc. Loughborough PCG London PCG Loughborough PCG Luton PCG Loughborough PCG London PCG Cornwall PCGANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 173 Table 2 Some of the major events for which the Group has had responsibility I n tern d o n a1 s ymp osia- 197 I lntcrnational Symposium on Liquid Scintillation Counting-Brighton 1973 International Symposium on Liquid Scintillation Counting-Brighton 1975 International Symposium on Liquid Scintillation Counting-Bath 1977 International Symposium on Liquid Scintillation Counting-Bath lY80 lntcrnational Symposium on Modern Radiochemical Practicc-York I984 International Symposium on Nuclear and Radiochemistry-Lindau 1986 Environmental Radiochemical Analysis-Fifth Symposium-Harwell 1988 International Symposium on Nuclear and Radiochemistry-Brighton I990 Environmental Radiochemical Analysis-Sixth Symposium-Manchester Liquid scintillation counting workshops- 1979 Queen Elizabeth College, London 1981 Salford University, Salford 1983 Queen Elizabeth College.London 1985 University of Technology, Loughborough 1987 University of Technology, Loughborough 1989 University of Technology, Loughborough Yourig persons research meetings- 1982 Salford Univcrsity 1984 Imperial College. London 1986 Birmingham University, Birmingham 1988 Imperial College. London 1990 University of Technology, Loughborough cussed ways of improving the dissemina- Table 3 Radiochemical Methods Group-past and future meetings Date 12 Nov, 1986 25 Nov. 1986 14-18 Sept, 1987 11 Nov, 1987 4 May, 1988 15 June, 1988 11-15 July, 1988 9Nov, 1988 22 Feb. 1989 4-8 Sept. 1989 26-28 Sept. 1989 15 Nov. 1989 17 May, 1990 12 Sept, 1990 19-21 Sept, 1990 13-14 NOV, 1990 13 Feb, 1991 4Apri1, 1991 15 May, 1991 2-6 Sept, 1991 13 Nov, 1991 May, 1992 Title Implementation of the New Ionising Radiations Regulations 1985 Chemical Aspects of Radioactive Waste Disposal Liquid Scintillation Counting Workshop Radioimmunoassay and Labelled Antibodies The Training of Radiochemists Young Researchers Meeting The 2nd International Conference on Nuclear and Radiochemistry Assuring Quality in Radiochemical Analysis Environmental Radioactivity Liquid Scintillation Counting Workshop SAC Meeting Radionuclide Measurement and The Chemistry of Radioactive Young Researchers Meeting International Symposium- Characterization Waste Disposal Environmental Radiochemical Analysis Labelling with Radioisotopes Applications and Uses of Radioisotopes in Medicine Joint meeting with Scottish Region-student meeting Non-radiometric Methods of Measuring Radionuclides Liquid Scintillation Counting Workshop European Radiochemistry Monitoring the Radionuclides in the Estuarine Environment Venue Harwell, London Oxfordshire Loughborough Amersham London London Brighton We ybridge Harwell Loughborough Loughborough Risley Strat hclyde Loughborough Manchester Winfrith London Glasgow Harwell Loughborough Loughborough Edinburgh tion of information to members of the Group and also ways of attracting new members to the Group.Feedback from the membership is currently by participa- tion in organized events. Written and oral communications from members are encouraged after each meeting. Of real concern is the demise of teach- ing of radiochemistry in higher education. Few universities now offer radiochemistry in their syllabi. There is little doubt that there remains a need for training of radiochemists and that, in part, the Radiochemical Methods Group fulfils this need by providing a stimulating pro- gramme of events. Some thought has been given to the provision of ‘master classes’ in various radiochemical methods, but these have yet to be formal- ized.

ISSN:0144-557X    

DOI:10.1039/AP991280169b

出版商:RSC    

年代:1991

数据来源: RSC

摘要:

174 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 Presentation of AnalaR Medal BDH Laboratory Supplies, a division of Merck Ltd., presented the Third AnalaR Gold Medal to Professor D. Thorburn Burns, of The Queen’s University of Belfast, at a dinner held at the Royal Society, London, in February. The medal is awarded triennially in recognition of a ‘meritorious contribution in the field of analytical chemistry which has had an important effect on the development of analytical techniques’. The photograph shows Professor Burns (R) receiving his medal from Dr. Roger Perry, a director of the Merck Laboratory Group.

ISSN:0144-557X    

DOI:10.1039/AP991280174b

出版商:RSC    

年代:1991

数据来源: RSC

摘要:

ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 175 Analytical Viewpoint The following is a member of a continuing series of articles providing either a personal view of part of one discipline in analytical chemistry (its present state, where it may be leading, etc.), or a philosophical look at a topic of relevance to chemists i n general or analytical chemists in particular. These contributions need not have been the subject of papers at Analytical Division Meetings. Persons wishing t o provide an article for publication i n this series are invited t o contact the editor of Analytical Proceedings, who will be pleased t o receive manuscripts or t o discuss outline ideas with prospective authors. Comparison of Coprecipitation and Chelating Ion Exchange for the Preconcentration of Selected Heavy Metals From Sea-water Michael N.Quigleyt and Frederick Vernon* Department of Chemistry and Applied Chemistry, University of Salford, Salford M5 4 WT Coprecipitation with hydrated iron(iii) oxide and chelating ion exchange with Chelex-100 resin have found widespread use in the preconcentration of trace metals from sea-water. Both methods offer advantages and disadvantages. Chelex-100 is best used for the processing of large volumes of sea-water but assessment of results must be made with care since a number of problems are apparent. (a) Florence and Batley noted that for some metals, a significant fraction exists in a form which makes chelating ion exchange impossible.' They observed that recovery of an ionic spike by Chelex-100 may bear no relation to the recovery of a metal naturally present in sea-water.These comments have been substantiated by other workersz-4 and are confirmed in the present study. Ultraviolet oxidation of sea-water is the only effective means of increasing the concentration of chelatable species.'-' (b) The resin may become saturated with alkali and alkaline earth metals.8-1 I ( c ) High concentrations of eluted alkali and alkaline earth metals may interfere with the subsequent trace metal analysis unless already removed. 12 Although ammonium acetate buffer solution is known to remove Mg'+ and Ca'+ ions from the resin," some metal ions of interest ( e . g . , Cu2+ and Mn'+) are also eluted.l"I4 ( d ) In certain instances, trace metals may be difficult to desorb.1' ( e ) Too high a flow rate of sample through a column of Chelex-100 may lead to inefficient ex traction of trace metals .7 Hydrated iron(iii) oxide can be used most effectively in small batch scale operations but suffers from problems during filtration and, of course, cannot be used for the determination of iron itself.Difficulties with contamination of the reagents used to prepare the precipitate must also be taken into account. Methods of reductive precipitation16 and chelating ion exchangel7 have proved successful for the preconcentation of trace metals prior to spectrophotometric analysis but are labour intensive. Coprecipitation with hydrated iron(iii) oxide or chelating ion exchange with Chelex-100 remain, however, the most effective methods of preconcentration. Experiments were performed to compare the effectiveness of coprecipita- tion and chelating ion exchange for the preconcentration of cadmium, cobalt, copper, manganese and nickel from North Wales coastal sea-water prior to determination by electro- thermal atomic absorption spectrophotometry (AAS).* To whom corrcspondcncc should be addressed. .t Prcsent addrcss: Dcpartmcnt of Chemistry, Chevron Science Ccntcr. Univcrsity o f Pittsburgh, Pittsburgh, PA 15260, USA. Experimental Sea-water was collected in acid-washed, 20 1 polypropylene containers on a rainless day from the shore at Llanddulas (East and West beaches) and Abergele, North Wales. The method of Harvey,Ix recommended by Martin,'" was used to determine the salinity. The figure of 33.15%0 obtained suggests there was little influence by estuarial or meteorological dilution.In addition, the pH was determined to be 8.1. Before storage and subsequent metals analysis, the sea-water was filtered through a 0.45 pm membrane filter and acidified to pH 2 with hydrochloric acid solution.") As speciation analyses were not intended, no further treatment of the sea-water was carried out. By using an Instrumentation Laboratory 351 atomic absorp- tion spectrophotometer, 555 graphite furnace and pyrolytic graphite cuvettes, the highest sensitivities for the trace metals were obtainable using the six-stage temperature programmes shown in Table 1. Instrument conditions of the IL 351 spectrophotometer were set as follows: Cd, 228.8 nm wavelength, 3 mA lamp current, 1 nm bandpass; Co, 240.7 nm wavelength, 10 mA lamp current, 0.3 nm bandpass; Cu, 324.7 nm wavelength, 5 mA lamp current, 1 nm bandpass; Mn, 279.5 nm wavelength, 5 mA lamp current, 0.3 nm bandpass; Ni, 232.0 nm wavelength, 10 mA lamp current, 0.15 nm bandpass.Table 1 Temperature programmes used for determination of trace metals in sea-water Mctal Dry Ash Atomize Tim& Cd 20 25 25 5 - - TcmpcraturcPC 75 100 420 2000 - - Tim& Cd 20 25 35 10 0 s Time/s c u 20 2s 1s 1s 0 5 Temperature/"C 75 100 550 750 1800 - Time/s Mn 20 25 20 20 0 5 TemperaturePC 7s 100 400 600 2000 - Time/s Ni 20 25 15 15 0 5 TemperaturePC 7s 100 475 600 1950 - Tcmpcrature/"C 75 100 450 950 2200 - Coprecipitation of Trace Metals in Sea-water With Hydrated Iron(n1) Oxide The following single precipitation technique was duplicated using analytical grade reagents: 5 ml of 2000 mg 1 - 1 Fe3+ solution were pipetted into a beaker containing 1 1 of176 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 sea-water, stirred and ammonia solution was added to adjust the pH to 9.The final iron concentration was approximately 10 mg 1 - 1 of Fe3+. The solution was then left overnight. The precipitate was collected by filtration by using a 0.45 pm membrane filter and the Fe(OH)3 loaded membrane trans- ferred to a 100 ml beaker. Then 2 ml of concentrated nitric acid were added in order to dissolve the precipitate. This solution was finally diluted to 50 ml in a calibrated flask. The concentration step for iron and coprecipitated trace metals was X20. In order to take account of any contamination from the addition of the iron reagent and ammonia solution, blank solutions of the reagents in distilled water were also prepared.Solutions were analysed for trace metals by use of electrother- mal AAS and the method of standard additions (10 pl sample injection size). A series of experiments showed that 1 pg 1-1 spikes of cadmium, cobalt, copper, manganese and nickel in synthetic sea-water could be coprecipitated with 95,92,95,75 and 81% recovery, respectively.21 Results for trace metal concentration in sea-water, corrected to take account of the percentage recovery, are given in Table 2. Table 2 Comparison of trace metal concentrations in North Wales coastal sea-water derived from coprecipitation and chelating ion exchange preconcentration Concentration of trace metals/yg 1-1 Method concen- tration Metal ( i ) (ii) (i) (ii) ( i ) (ii) Fe(OH)3 Cd 0.67 0.67 0.64 0.64 0.53 0.54 Chelex-100 0.55 0.54 0.44 0.45 0.42 0.42 Chelex-100 0.19 0.11 0.11 0.10 0.11 0.11 Chelex-100 3.7 3.4 2.1 2.4 2.6 2.4 Fe(OH)3 Mn 54.0 53.6 5.7 5.7 4.9 4.9 Chelex-100 25.5 27.4 3.9 4.0 2.7 2.9 Fe(OH)3 Ni 3.1 3.2 3.2 3.3 3.5 3.3 Chelex-100 2.5 2.3 2.5 2.8 2.5 2.6 of Abergele Llanddulas E.Llanddulas W. Fc(OH)~ CO 0.54 0.56 0.53 0.59 0.54 0.53 Fc(OH)3 CU 5.5 5.7 3.2 3.4 3.5 3.7 Chelating Ion Exchange of Trace Metals in Sea-water With Chelex-100 Protonated (H+) form Chelex-100 (Bio-Rad Laboratories) was purified by washing with 2 mol 1-1 nitric acid solution and distilled water. The resin was converted to the NH4+ form by soaking in 2 mol 1-1 ammonia solution.Peristaltic flow ion- exchange columns were constructed such that sea-water was able to flow upwards to increase the contact between the sea-water and resin. The columns were of length 45 mm, bore 16 mm, one end of which was drawn out to a 3 mm bore. A flexible tube and clip completed the assembly. The lower end of the column was plugged with acid-washed glass wool and the column was filled with 6 ml of settled NH4+ form Chelex-100. Another plug of glass wool was placed on top of the resin and the column sealed with a rubber stopper carrying another length of flexible tubing. Distilled water was passed through the column at a flow rate of 0.8 ml min-1 to clean the resin further before use. The pH of the sea-water was adjusted to pH 5 with ammonia solution before passage through the column.In terms of volume of resin, the metals should have been concentrated by a factor of 167, assuming quantitative adsorp- tion. The resin was next washed with 10 ml of distilled water, followed by two 5 ml volumes of 2.5 moll-' nitric acid solution. The eluate was collected in a 50 ml calibrated flask. The concentration step for trace metals was ~ 2 0 . Dilutions (1 + 9) were prepared for analysis by electrothermal AAS using the method of standard additions (10 pl sample injection size). A similar procedure using distilled water was followed to prepare a blank solution. Results are given in Table 2. Conclusion With reference to Table 2, it can be seen that there is a fairly close agreement between the concentrations of all metals preconcentrated by either coprecipitation or chelating ion exchange. In all instances, the concentration of metals eluted from the column of Chelex-100 resin was determined as being slightly lower than those obtained after dissolving the hydrated iron(ii1) oxide with nitric acid.This is probably a result of the problems of non-chelatable species present, inefficient desorp- tion and alkali and alkaline earth metal saturation of the resin mentioned earlier. To a first approximation, however, the two methods give the same results. The concentration figures are of the right order for coastal sea-water,22 although those obtained for manganese in Abergele coastal sea-water are probably influenced by terrestrial sources of contamination. If an analytical method requires a large concentration of trace metal for analysis, then preconcentration by passage of sea-water through a long column of regularly regenerated NH4+ form Chelex-100 is recommended.For simplicity and convenience, hydrated iron(ii1) oxide is better suited to small batch scale operations. Editing and typing of the manuscript by Lisa A. Alzo is greatly appreciated. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 References Florence, T. M., and Batlcy, G. E., Talanta, 1976, 23, 179. Florence, T. M., and Batley, G. E., Talanta, 1977, 24. 151. Muzzarclli, R. A. A., and Rochctti, R., A n d . Chim. Acta, 1974. 69. 35. Abdullah. M. I.. El-Rayis, 0. A., and Riley. J . P., Anal. Chim. Acta, 1976. 84, 363. Sturgeon, R. E.. Bcrman. S. S . , Dcsaulnicrs, A., and Russell, D.S., Talanta, 1980, 27, 85. Brugmann, L., Danielsson, L.-G., Magnusson, 9.. and Wester- lund, s.. Mar. Chem.. 1983, 13. 327. Paulson, A. J.. Anal. Chem., 1986, 58, 183. Van Grieken, R. E., Bresscleers, C. M., and Vanderborght, B. M., Anal. Chem., 1977, 49, 1326. Ashton, A., and Chan, R., Analyst, 1987, 112, 841. Bruland, K. W.. Franks, R. P., Knaucr, G. A., and Martin, J. H., Anal. Chim. Acta, 1979, 105, 233. Abdullah, M. I . , and Roylc, L. G., Anal. Chim. Acta, 1972.58, 283. Kingston, H. M., Barnes, I. L . , Brady. T. J . , Rains, T. C., and Champ, M. A., Anal. Chem.. 1978, 50. 2064. Cheng, C. J.. Akagi, T., and Haraguchi, H., Bull. Chem. SOC. Jpn.. 1985, 58, 3229. Sturgeon, R. E., Berman, S. S . , Desaulniers, J. A. H., Mykytiuk, A. P.. McLaren, J. W., and Russell, D. S . , Anal. Chem., 1980, 52, 1585. Riley. J. P., and Taylor, D., Anal. Chim. Acta, 1968, 40, 479. Skogerboe, R. K., Hanagan, W. A., and Taylor, H. E., Anal. Chem., 1985, 57, 2815. Samara, C., and Konimtzis, T. A., Anal. Chim. Acta, 1985, 174, 305. Harvey, H. W., The Chemistry and Fertility of Sea Waters. Cambridge University Prcss, London, 2nd edn., 1957. Martin, D. F., Marine Chemistry, Marcel Dekker, New York, 2nd cdn.. 1972, vol. 1, p. 89. Jones, K. C.. Peterson, P. J . , and Davies, 9 . E., Int. .I. Environ. Anal. Chem.. 1985, 20. 247. Vernon, F.. and Quiglcy, M. N., unpublished results. Riley, J. P., Robertson, D. E., Dutton, J. W. R., Mitchell, N. T., and Williams, P. J. le B., in Chemical Oceanography, eds. Riley, J. P., and Skirrow, G., Academic Press, London, 2nd edn., 1975, vol. 3, pp. 343-392.

ISSN:0144-557X    

DOI:10.1039/AP9912800175

出版商:RSC    

年代:1991

数据来源: RSC

摘要:

ANALYTICAL PROCEEDINGS, JUNE 1991. VOL 28 Biomedical and Pharmaceutical Chemistry 177 The following are summaries of seven of the papers presented at the analytical symposium at the RSC Autumn Meeting held on September 25th-27tht 1990, in the University of Keele. Implications of Regulatory Requirements for Bioanalytical Techniques and Resources Colin W. Vose Hoechst UK, Walton Manor, Milton Keynes MK7 7AJ The regulatory requirements for drug approval can be sum- marized as ‘demonstrate the efficacy and safety of the drug in treating the disease’. The time course (pharmacokinetics) of a drug and/or its metabolites influence its efficacy and safety, and pharmacokinetic data are thus essential for drug R & D. To generate valid pharmacokinetic data, analytical methods for a drug and/or metabolite(s) are required that have adequate precision (RSD < 15%), accuracy (90-1 lo%), sensitivity (to follow concentrations for about four half-lives) and specificity (ideally 100% specific).These assay characteristics must be clearly defined in a formal assay validation for each sample matrix (plasma, urine, etc.) that is to be analysed. In addition, the stability of the analyte must be established under the collection and storage conditions for each matrix. Bioanalytical Workloads in Drug R & D Method development and validation can take between 3 and 12 months, depending on the technique, the sensitivity required and the biological matrices. In routine application the ideal is analysis and reporting of results within 2-3 months of sample receipt.In our laboratories, routine bioanalysis has increased from 2446 samples per year in 1975 to 24643 samples per year in 1989. The largest increase has been in clinical samples (20 000 in 1989 versus 800 in 1975). The development of a given drug may involve the analysis of about 36000 samples (plasma, urine, etc.) for the drug and, where appropriate, metabolites. As routine assays require calibration and quality control samples, a total of 45000 analyses will be required for each analyte. Assuming 300 analyses per week in a 46 week year, allowing for holidays and sickness, this represents 3.3 man-years of work and at f25 per assay this represents about f l . 1 million. These workloads, time and costs mean that inappropriate application of bioanalytical resources will waste time and money and may delay progress with other projects competing for this limited analytical capacity.Some examples of control- ling this competition and usage are presented. Minimizing the Number of Analytes and Avoiding Speculative Assay Development Gas chromatographic assays were available for an aldehyde- containing drug and its carboxylic acid metabolite in plasma. Radiolabelled metabolism studies in animals showed that the drug, the carboxylic acid and its ester glucuronide were important urinary components. This suggested that urinary assay methods would be needed for all three in man, a significant additional workload. Direct proton NMR analysis of urine from subjects receiving 200mg single oral doses in a tolerance study showed no detectable parent drug (no aldehyde signal) but high levels of carboxylic acid and glucuronide. This information avoided the need to develop and validate an assay for the parent drug.Developing Multiple Analyte Assays if Possible The determination of oxpentifylline and its side-chain hydroxy- lated metabolites (Fig. 1) was required in order to investigate kinetic-dynamic relationships. A simple extraction, derivatiza- tion and capillary GC assay with nitrogen-phosphorus-specific detection was developed by Burrows and Jolley’ that allowed the simultaneous determination of the drug and its four metabolites at levels down to 1-2 ng ml-1 in human plasma. It had appropriate accuracy, precision and specificity (Fig. 1, Table 1). This allowed the essential concentration data on the drug and its four metabolites to be determined very efficiently in a single assay.Selecting the Simplest and Highest Throughput Assays The parallel development of an immunoassay with a chromato- graphic method should always be considered. A GC assay with electron-capture detection (ECD) had been developed for a Table 1 Determination of oxpentifylline (I) and its metabolites (II-V) added to blank plasma. In all instances n = 6. with VII used as an internal standard Approximate Conccntration foundhg ml-l concentration addcdlng m l ~ 1 I 11 I I I t IV V 0 0 f 0 0.4 f 0.5 23.5 k 3.3 0 f 0 1 . 4 f 1.6 5 5.9 f 0.7 6.3 f 0.8 32.3 2 5.9 4.8 k 0.3 6.2 -t 0.8 SO 49.3 t 0.9 52.0 t 3.2 70.1 2 8.2 50.1 k 2 . 8 50.8 -t 4.5 500 522 2 5 538 t 21 527 & 28 523 2 24 516 -+ 26 2500 2570 f 59 2582 t 201* NS$ NS NS * n = S .-t Interference in control plasma absent from real samples. $ NS = No samples.178 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 dH3 R’ R2 I1 CH3CH(OH)CH2 CH3 111 HOCHZCH(OH)CH2 CH3 IV CH,CH(OH)CH(OH) CH3 V CH,CH(OH)CH(OH) CH3 VI HOCH2CHzCH2 CH3CH2CH2 VII CH3COCH2CH2 CH3 I CH3COCH2 CH3 Fig. 1 Structure of oxpentifylline and metabolites Table 2 Comparison of radioimmunoassay (RIA) and GC-ECD assays GC KIA Limit of determination (ng ml- 1) 5 0.2 Samplc throughput (No. per week) 80 400 Accuracy (% of target value) 90-1 10 90-1 10 Assay range (ng ml-1) 5400 0.2-200 Precision [RSD. (%)I 4-1s 3-19 Continuous Automation Over the past 20 years, automation of bioanalytical procedures has progressed rapidly.We have about 20 chromatographs (GC and HPLC) each of which is equipped with 100 sample capacity autosamplers. Each system is linked to a central automatcd data collection and analysis system. Reviewed and audited analytical reports can be issued via electronic mail. A parallel system exists for immunoassays. The availability of automated sample preparation systems, e.g., Zymate robot, ASPEC and ASTED, meanS that the entire process from sampling to report generation can be automated, a process that resources. drug, involving a complex series of solid phase and solvent extraction procedures followed by derivatization. A radio- performance characteristics shown in Table 2. The immuno- assay tended to overestimate drug levels relative to the GC method. However, its greater sample throughput and sensi- tivity made it the assay of choice for supporting phase I1 clinical studies.187. immunoassay had also been developed* The two assays had the will continue with the ever increasing demands on bioanalytical Reference 1 Burrows, J . L., and Joky. K . W., J. C/ir.ornarogr.. 1985, 344. Liquid-Liquid and Liquid-Solid Phase Extraction as Applied to the Determination of Drugs in Biological Samples Robin Whelpton Department of Pharmacology, Queen Mary and Westfield College, Mile End Road, London E I 4NS Choice of Solvent for Liquid Extractions In principle, liquid-liquid extraction is extremely simple. An aqueous solution of the drug is ,shaken with an immiscible organic solvent and, if the conditions have been chosen correctly, the drug partitions such that it is almost entirely in the organic phase.Before embarking on a particular method, it is worth considering why some solvents may be useful and others best avoided. Naturally, the final choice will depend on the properties of the analyte(s) and the method of analysis to be used. Polarity is almost synonymous with ‘extraction power’-the greater the polarity of the solvent, the more compounds are extracted. What Brodie et aZ.1 said on the subject over 40 years ago is still true: ‘The solvent of choice is . . . the least polar one which will extract the compound quantitatively’. This should give the maximum selectivity. We start by trying hexane or heptane and work through a range of solvents such as toluene, diethyl ether, ethyl acetate and chloroform until a suitable solvent is found.Boiling-point is an important consideration if the solvent is to be evaporated, when a low boiling-point solvent may be an advantage; for example, we would use hexane rather than heptane. On the other hand, evaporation of very low-boiling solvents, such as diethyl ether, during handling may cause problems with accurate determination. The solvent should be ‘transparent’ to the method of analysis. For example, strongly UV-absorbing solvents should be avoided if UV detection is to be used. Chlorinated solvents are contra-indicated if radioactive scintillation counting or GC with elcctron-capture detection is to be used. Some solvents, or impurities in them, may react with the analyte. Obviously, aldehydes and ketones will react with primary amines and the amounts of peroxides in ethers may be sufficient to oxidize sensitive compounds.We encountered a problem with a primary amine metabolite of chlorpromazine that was shown to be condensing with isovaleraldehyde, which was an impurity in thc isopentyl alcohol’ being used to reduce adsorption on glassware. Liquid Extraction of Weak Electrolytes and the Use of Computer Programs Many drugs are weak electrolytes and the pH of the aqueous phase may be optimized to control the extraction into the organic phase. The fraction, f , extracted into the organic layer is given by j = [ I + VJ(V0Pa)]-’ where V , and V,, are the volumes of the aqueous and organic phases, respectively, and P;, is the apparent partition coef- ficient of the solute.P , is a function of the true partition coefficient, P,, and the pK,, of the ionizing group and the pH of the aqueous phase. For a base, P, = P;, [l + 10(PKa - PH)] Generally P, is unknown and pK, may be unknown or in doubt, which leaves two unknown variables. However, these can be estimated from iterative curve fitting of P , versus pH data.3 Once P, and pK, are known, the percentage extracted can be calculated for any organic to aqueous volume ratio and any pH value. By knowing the pH-extraction characteristics of a drug and its important metabolites, extraction schemes can be optimized and often a drug may be separable from its metabolites and/or interfering substances. This is the approach we used with 14C-labelled fluphenazine ,3 when it was possible to separate fluphenazine , fluphenazine sulphoxide and 7-hydroxyfluphen-ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 179 azine into three separate fractions by the judicious use of organic solvents and pH.Solid-phase Extraction of Drugs Solid-phase extraction offers several advantages over liquid- liquid extraction but it is not without problems of its own. It is often possible to develop solid-phase extraction methods that do not require such extreme pH values as liquid extraction. This may be important for pH-sensitive analytes. Quatcrnary ammonium compounds, e.g., pyridostigmine and paraquat, can be extracted easily, thus obviating the need for ion-pair extraction methods. Large volumes of dilute aqueous solutions can be quickly concentrated on solid-phase columns.By concentrating on columns followed by elution into the mini- mum volume of eluent, it is possible to avoid concentration by evaporation, a stage which frequently causes problems in liquid-liquid methods. Obvious disadvantages include blocking of the columns with particulate matter and poor retention of some compounds from biological samples. Centrifugation or filtration before samples are applied is helpful but this should be carried out after adjustment of the pH, as, for example, a white, gelatinous precipitate is produced when urine is made alkaline. Two problems that we commonly encounter with biological samples, which are not apparent when solutions in water are used, are poor recovery from urine, which appears to be due to competition with urine components, and reduced plasma recoveries due to protein binding.The best recoveries from urine are often obtained using the high-capacity CIS phases, but these retain very large amounts of urinary pigments such that the final eluate is bright yellow. For the HPLC analysis of hyoscine we retained it o n C18 and washed off the bulk of the pigment with methanol-water (2 + 8) (checking to ensure that this did not elute the analyte). Hyoscine was eluted with methanol-water ( 1 + 1) and the eluent was diluted 1 + 9 with water and reapplied to acid-prepared nitrile columns. The final elution was into a small volume of HPLC eluent. The 1 + 9 dilution was only necessary when the initial sample was urine; with aqueous samples hyoscine could be retained from methanol-water (1 + 1) eluent, which seems to indicate that the interfering substances are still present.If the recovery of a drug from plasma is reduced, and particularly if it is dependent on flow-rate, then protein binding should be suspected. Again, high-capacity columns may be required and the sample applied at a low flow-rate so that the drug can equilibrate with the solid phase.’ Diluting the sample (say 10-fold) with water can help. Problems with biological samples can be minimized by combining liquid-liquid- and liquid-solid-phase methods. This is an approach we are increasingly adopting as it combines the best of the two methods. For example, for prilocaineh we extracted alkaline plasma with toluene and adsorbed the drug on acid-washed diol AASP cartridges. The prilocaine was eluted with an acidic HPLC eluent.This approach avoids the problems associated with solid-phase extraction (particulate matter, urinary pigments, protein binding) and liquid-liquid extractions. Conclusion Despite its age, liquid-liquid extraction remains a very valuable sample preparation technique for drug analysis, particularly if a systematic approach is adopted and iterative computer programs are applied where appropriate. For some analytes, particularly polar types, solid-phase methods may be better, but the best approach may be to combine the two methods . References 1 Brodie, B. B., Udenfriend, S . . and Baer, J. E . . J . Biol. Chem., 1947, 158. 299. 2 Whclpton, R . , and Curry. S. H., J . Chromatogr.. 1976, 121. 88. 3 Whelpton. R.. Trends Pharm.Sci., 1989, 10, 182. 4 Whelpton. R., and Curry, S. H., Methodol. Surv. Biochem. Anal., 1976, 5, 115. 5 Whelpton, R., and Hurst, P. R.. Methodol. Surv. Biochem. Anal.. 1988, 18, 289. 6 Whelpton. R . . Dudson. P., Cannell. H.. and Webstcr, K., J . Chromatogr., 1990, 526, 215. Use of Mass Spectrometry in Pharmaceutical Analysis Alison E. Ashcroft ICI Pharmaceuticals, Safety of Medicines Department, Modern mass spectrometers offer the discerning analyst a wide array of chromatographic interfaces, ionization techniques and scan functions, all of which must be taken into consideration before embarking on an analysis. The demands of the sample in terms of polarity, volatility, relative molecular mass, purity and amount available will largely determine the instrumental conditions used to obtain the information required.Mass spectrometry i n the pharmaceutical industry encom- passes a wide range of samples and different types of data are required at different stages of the drug discovery programme. At the beginning of this programme, a large number of potential drugs are synthesized by research chemists, and the samples submitted for mass spectrometric analysis usually consist of a single component in milligram amounts. The fastest way to analyse this high throughput is by direct introduction of the samples into the ionization source of the mass spectrometer on an insertion probe. The ionization technique employed will depend on the polarity and volatility of the sample, and will probably be electron impact, chemical ionization or fast atomhon bombardment.The relative molecular mass of the sample will be verified, and occasionally the formula deter- mined, by an accurate mass measurement. A select few of these synthetic products will be taken further Alderle y Park, Macclesfield SK 10 4TG and submitted to extensive testing with the aim of finding a ‘safe’ drug with high efficacy. The pharmacokineticists require assays for these compounds and often their major metabolites. These assays involve the specific detection of one or two previously identified components in a multi-component sample at very low detection limits, GC-MS is often the method of choice-after derivatization of the more polar components- with electron impact or positive or negative chemical ionization depending on the nature of the sample, and selective ion monitoring of a few pertinent ions rather than complete scanning.Metabolite identification involving the characterization of very polar, unknown compounds available only in small amounts in complex samples is also achieved by mass spec- trometry, in conjunction with other spectroscopic techniques. The most popular technique here is LC-MS with thermospray, fast atomhon bombardment or electrospray ionization. These ‘soft’ ionization techniques sometimes produce solely quasi- molecular ions, and hence relative molecular mass informa- tion, and MS-MS analysis is used to obtain specific fragmenta- tion patterns from which structural information can be deduced. For the few selected compounds which are successful as180 01 .; 0 + 100 K ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 A I I 1 I I 467 I h m/z 194 - drugs, mass spectrometry is required in order to check the quality of the bulk drug and to detect and identify any impurities arising during the manufacturing process; LC-MS and MS-MS are again vital techniques.The use of LC-MS and MS-MS in metabolite identification is described below for a recent example in this Department. 0 $100 m/z 175-300 .- 5 B g o - 100 +I I I I I I .- m/z180 m/z 228 loo" 0 0 r I z z i l 100 200 300 400 500 600 700 m/z UV and mass chromatograms for the male urine sample Fig. 1 Experimental A VG Trio-3 tandem quadrupole mass spectrometer, equipped with a combined thermospraylplasmaspray LC-MS ionization source operating in the positive ion mode, was used with a probe temperature of 280 "C and a discharge of 1000 V.Aqueous acetonitrile (20%) containing 0.1% of trifluoro- acetic acid was passed through an ODS column (25 cm x 4.6 mm i.d.) at a flow-rate of 1 ml min-1 to effect the separation. A UV detector operating at 254 nm was situated in-line with the mass spectrometer. For the MS-MS experiments, argon as collision gas was introduced into the hexapole collision cell until the parent ion was attenuated by 30%. A collision energy of 5 eV optimized the daughter ion spectrum. Results and Discussion As part of the development programme for the drug (I) a sample was dosed to a male volunteer. The urine sample, after COOH I work-up, showed evidence of the presence of several com- ponents. Plasma spray LC-MS analysis carried out with a UV detector in-linc showed very similar mass spectrometric and UV chromatograms for the urine sample, and at first glance the sample appeared to be composed of three chromatographic peaks with retention times of 1 min 56 s, 8 rnin 54 s and 11 rnin 27 s (Fig.I ) . Inspection of the spectra of these peaks showed the first peak to have a significant ion at mlz 180, the second to have two significant ions at rnlz 194 and 210 and the third an ion at mlz 228. This implies the presence of components with relative molecular masses of 179, 193, 209 and 227 u, respectively. The co-elution of two components at 8 rnin 54 s was confirmed by MS-MS experiments showing that the two ions at rnlz 194 and 210 were unrelated. None of the parent drug ( M , 402 u) was detected. Little structural information for these four compounds could be determined from the spectra.Apart from relative molecular masses the other piece of information deduced was that the component at 11 rnin 27 s showed an isotope pattern typical of a monochlorinated species (Fig. 2). To obtain structural infor- mation on these compounds, MS-MS daughter ion spectra were acquired from each of the four protonated molecular ions. I 90 loo 1 3 50 < 40 30 U 20 10 0 .- .I- 120 140 160 180 200 220 240 260 280 300 m/z Fig. 2 1 1 rnin 27 s Mass spectrum of the later running component. retention time Fig. 3 shows the MS-MS daughter ion scans from rnlz 228 and 230 of the monochlorinated component. Both show losses of 32 and 89 u, and the more intense parent ion (mlz 228) shows an additional loss of 60 u.The chlorine atom is retained in all of these fragmentations. 100 50 0 100 50 0 20 40 60 80 100 120 140 160 180 200 220 240 m/z Fig. 3 rnlz 230 (upper trace) MS-MS daughter ion spectra from rnlz 228 (lower trace) and The daughter ion scan from rnlz 180 showed a loss of 75 u, leading to an ion at rnlz 105, which in turn fragmented with loss of 28 u to produce an aromatic ion at mlz 77. The daughter ion scan from mlz 194 showed ions at rnlz 162, 134 and 105, indicating losses of 32, 60 and 89 u, respectively; the daughter ion scan from rnlz 210 showed a loss of 89 u with a daughter ion at rnlz 121. From these data, it appeared that the four components were members of a closely related series differing in the substitution pattern of a benzyloxy derivative.The peak eluting at 1 min 56 s with a relative molecular mass of 179 u was identified as hippuric acid, and one component from the peak eluting at 8 rnin 54 s its methyl ester (relative molecular mass 193 u). The co-eluting component at 8 rnin 54 s is a hydroxylated derivative of methyl hippurate (relative molecular mass 209 u) and the later running peak at 11 min 27 s, found to be the only drug-related material present in the sample by virtue of its radiolabel, is the chlorinated derivative 11. Final confirmation of this glycine conjugate was achieved by comparison (LC-MS, LC-MS-MS) with an authentic standard at a later date. Methylation to produce the methyl ester components isANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 181 0 Conclusion LC-MS-MS has been used to identify a drug metabolite in a mixture of similar, but non-drug-related, compounds and to achieve the separation of two co-eluting components.II thought to have taken place during work-up of the urine sample. Dr. I. D. Wilson and his unit are thanked for providing the sample and for useful discussions. High-resolution Nuclear Magnetic Resonance Spectroscopy of Biofluids and Applications in Drug Metabolism Jeremy R. Everett Analytical Sciences, Smith Kline Beecham Pharmaceuticals, Brockham Park, Betch worth, Surrey RH3 7AJ Biological NMR Spectroscopy The application of NMK spectroscopy to biological samples is now a vast field of endeavour that embraces a number of different areas. I n order of increasing biological complexity of the 'samples', these areas are NMR spectroscopy of biological macromolecules, of biofluids, of cell and tissue extracts, of isolated cells of isolated organs and tissues, and whole-body NMR spectroscopy or magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI).NMR spectroscopy is unique in its ability to study biological systems as simple as a solution of a single protein molecule or as complex as a whole human being; the non-invasive nature of NMR is the key to its success in many of these biological applications. NMR Spectroscopy of Biofluids The application of NMR spectroscopy to the study of biofluids has becn explored only over the past decade.' The range of biofluids that have been studied is large and includes urine, blood plasma, bile, seminal plasma, milk, cerebrospinal fluid, ascites, sweat, synovial fluid and tears.Properties of Biofluids The different biofluids have characteristic physicochemical and biochemical properties and it is necessary to take account of these in the design of biofluid NMR experiments.' For instance, each biofluid has a characteristic profile in terms of the relative concentrations of solvent water, protein and lipids. The presence of large concentrations of macromolecules such as protein and lipid in blood plasma gives rise to 1H NMR spectra in which the sharp resonances for the low relative molecular mass endogenous components are superimposed on the very broad 'rolling hill' macromolecule resonances. In order to study the low relative molecular mass components, it is necessary to eliminate the broad resonances, and this can be achieved by the application of spin-echo pulse sequences (90"-~-180"-~-acquire data).The broad lines of the macromolecules have short T2 relaxation times and their signals simply decay to zero in the T delays of the pulse sequence. Water Suppression The presence of water protons at concentrations of about 100 mol dm-3 in biofluids presents a problem of dynamic range for the detection of the 1H resonances of biofluid components present at millimolar concentrations or less. The simplest method of overcoming this problem utilizes gated irradiation at the water resonance in order to saturate it and reduce its intensity. This procedure can be fairly efficient and suppression factors of several hundred may be achieved.Why Use NMR Spectroscopy to Study Biofluids? Many analytical techniques are in routine use for the analysis of biofluids, so why use NMR spectroscopy additionally? The reasons are manifold and lie in the unique properties of NMR spectroscopy : 1. NMR is a non-selective detector that will monitor the levels of all low relative molecular mass biofluid components present in free solution, at concentrations above the detection threshold of about 10-100 pmol dm-3 (for 'H NMR spectroscopy at 400-500 MHz and variable according to the type of experiment). This is an important attribute in the search for novel metabolites, when often the analyst will have no idea of the type of molecule to look for. 2. The information content of biofluid NMR spectra is very high.A 600 MHz *H NMR spectrum of human urine contains resolved signals for hundreds of endogenous biofluid components, many of which are of considerable biochemical significance. In addition, 'H NMR spectra of biofluids give characteristic patterns of signals which themselves carry important biochemical and physiological information.' 3. Sample throughput in NMR spectroscopy is fast and lH NMR spectra can be obtained in 5 min or less. 4. NMR spectroscopy is non-destructive and requires low sample volumes (0.35 ml minimum), which allows the spectroscopist to work with difficult-to-obtain biofluids such as those from neonates or small laboratory animals. 5 . Little or no sample preparation is required, other than the addition of a small amount of D20 to the sample (typically about 50 PI) in order to 'lock' the magnetic field.NMR spectroscopy is thus particularly suited to the study of delicate samples or of systems in equilibrium. 6. NMR spectroscopy gives direct structural information on all the molecules it detects in a biofluid, by virtue of the structural information carried in the chemical shifts, coupling constants and relaxation times. Set against these advantages, however, are a number of disadvantages which need to be taken into account, including the following: 1. NMR spectrometers are expensive instruments, with the cost rising steeply with the field strength of the magnet used. 2. Spectral crowding is a factor that often causes difficulties in the NMR detection of biofluid components, especially for 'H NMR spectroscopy, which has a very narrow spectral range.This problem can be minimized by operating at the highest available magnetic field strengths, currently 9.4-14.1 T and corresponding to 1H resonance frequencies of 400-600 MHz.182 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 3. NMR spectroscopy is a relatively insensitive technique because the signal derives from only -1 in 105 of the molecules of the sample. 4. In a complex biofluid such as plasma which contains a high concentration of protein, certain biofluid components may be invisible to NMR spectroscopy because of protein binding, even if they are present at concentrations which exceed the detection threshold of the NMR experiment. However, in spite of these difficulties, NMR spectroscopy has now become a technique of demonstrated utility and of unique ability in the analysis of biofluids.Applications of Biofluid NMR Spectroscopy There are three major application areas of biofluid NMR spectroscopy: drug metabolism, toxicology and clinical chem- istry. The last two areas are concerned with the study of both normal and abnormal endogenous biofluid components, and this is mainly carried out by 1H NMR spectroscopy. In contrast, the study of drug metabolism by biofluid NMR spectroscopy is concerned exclusively with the study of ‘foreign’ or exogenous compounds in the biofluid and this can involve lH, 13C, lSN or 1gF NMR spectroscopy, although 13C and IsN NMR spectroscopy are normally only employed in the study of 13C- or 1W-labelled drugs. Use of Biofluid NMR in the Study of Drug Metabolism The non-selective detector characteristic of NMR spectroscopy is the key to its successful use in the study of drug metabolism.Many conventional analytical methods used in drug metab- olism studies require preselection of the analytical conditions, e.g., HPLC, and there is a danger that unexpected metabolites may be overlooked. The main drawback to the use of NMR spectroscopy is its inherent insensitivity, which restricts its use to the study of high dose compounds. At the Brockham Park Chemotherapeutic Research Site, the human antibiotics on which we work have maximum doses to man of up to several grams per day, so sensitivity is not a problem, and the following examples of studies on penicillin antibiotics are drawn from such work.C02Na Sodium ampicillin . P C02Na Ampicillin diketopiperazine HO Penicilloic acids (5R and 55) -*. ’*, C02 N a Studies on the Urinary Metabolites of Ampicillin in the Rat In the 1H NMR spectrum of control rat urine, the region from 0.4 to 1.7 ppm is relatively clear of endogenous component signals. This is fortunate because this is the region in which the sharp, paired, singlet gern-dimethyl resonances of penicillins and their metabolites occur. Fig. 1 shows the high-field region of the 400 MHz spin-echo NMR spectrum of the 3-6 h post-dose urine from a rat dosed intravenously with sodium ampicillin. The gem-dimethyl and H-3 resonances of ampicillin are clearly observed and are marked with circles. Three other pairs of sharp, singlet gem-dimethyl resonances are observed, marked with filled and open stars and with triangles, and these are due to the (5R)- and (5s)-penicilloic acids and the diketopiperazine (DKP) metabolites, respectively, Diketopiperazine had not previously been reported as a metabolite of ampicillin and this discovery was our first success with biofluid NMR spectro~copy.~ Since that time we have gone on to investigate the metabolism of a number of penicillins, penems and cephalosporins which have been in development in our laboratories.H-3 0 I Me ** I I I I 4.0 3.0 2.0 1 .o 6 , PPm Fig. 1 High-field region of the 400 MHz spin-echo 1H NMR spectrum of the 3-6 h post-dose urine from a rat dosed intravenously with sodium ampicillin. Key to assignment of the gern-dimethyl resonances: @, sodium ampicillin; *, (SR)-ampicillin penicilloic acid; *.(5s)-ampicil- lin penicilloic acid; and A, ampicillin diketopiperazinc Studies on the Urinary Metabolites of Flucloxacillin in the Rat For fluorinated drugs the problems of water suppression and spectral crowding found for 1H NMR spectroscopy can be overcome by the use of 19F NMR spectroscopy, as there are negligible levels of fluorinated endogenous metabolites and the chemical shift range of 19F is very large, about 1000 ppm. We have used both 1D and 2D 19F NMR spectroscopy to study the metabolites of flucloxacillin in the urine of rats. In addition to the detection of the drug and two known metabolites, the (5R)-penicilloic acid and the 5’-hydroxymethylpenicillin, our studies revealed the presence of the 5s isomer of the penicilloic acid, which was previously u n k n o ~ n .~ . ~ Conclusion In our experience, biofluid NMR spectroscopy is simple to perform, has a high information content and provides a very powerful tool, complementary to many of the conventional techniques, with which to probe the metabolism of high dose drugs. I thank my co-workers Keith Jennings, John Tyler and Gary Woodnutt and I also acknowledge many hours of fruitful and stimulating discussions with Ian Wilson and Jeremy Nicholson.ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 183 References 3 4 5 Everett, J . R., Jennings. K. R . . Woodnutt. G., and Bucking- ham, M. J., J. Chem. Sac., Chem. Commun., 1984, 894. Everett. J. R., Jennings, K . , and Woodnutt. G., J . Pharm. Pharmacol., 1985,37, 869. Everett, .I.R., Tyler, J. W.. and Woodnutt, G., J. Phurm. Biomed. Anal.. 1989, 7, 397. 1 Nicholson, J . K.. and Wilson. I. D.. Prog. Nucl. Magn. Reson. Spcctrosc., 1989, 21, 449. 2 Gartland, K . P., Sanins, S. M., Nicholson, J. K., Sweatman. B. C., Beddell, C. R., and Lindon. J. C.. NMR Biomed.. 1990.3. 166. Strategic Applications of Proton Nuclear Magnetic Resonance Spectroscopy in Clinical Biochemistry and Analytical Toxicology J. K. Nicholson Department of Chemistry, Birkbeck College, Gordon House, 29 Gordon Square, London WClE 6BT I. D. Wilson Department of Safety of Medicines, ICI Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire SKlO 4TG The application of nuclear magnetic resonance (NMR) spec- troscopy to the biosciences, particularly in the biomedical area, has evoked considerable interest , especially with respect to the dramatic progress that has been seen in the field of magnetic resonance imaging.However, the advent of high field Fourier transform NMR spectrometers, operating at field strengths of 9.4 T (400 MHz proton resonance frequency) or more, has also enabled NMR to be used for the study of complex biological fluids such as plasma, urine and bile. Proton (1H) NMR is particularly well suited to the determination of the many low molecular mass endogenous organic compounds present in biological fluids and an NMR ‘profile’ or ‘fingerprint’ of a sample can be obtained within a few minutes with minimal sample pre-treatment. 1 Indeed sample preparation can often be limited to the addition of a small amount (about 10%) of 2Hz0 to provide a field frequency lock for the spectrometer.2.3 The spectral fingerprint provided by 1H NMR can be of great utility for clinical and diagnostic purposes, as changes in the normal composition of major components, which can reflect abnormal metabolic and disease processes in the whole organism, are readily observed.Of course, NMR is relatively insensitive when compared with many other trace analytical techniques, especially chromatography, and components must be present in concentrations of >10 pmol dm-3, and preferably 50-100 pmol dm-3, to permit detection. Clearly the com- pounds must also possess a suitable group to provide an NMR ‘handle’ (e.g., CH, CH2 or CH3) to facilitate detection. There are many instances, however, when the absolute sensitivity of the technique is not an issue and where the manifold advantages of NMR more than compensate for the perceived shortcomings.In particular, NMR is capable of providing a general means for the detection of compounds in biofluids, subject only to the restrictions described above , irrespective of structure and physical or chemical properties ( i e . , the presence or absence of a chromophore, polarity, state of ionization, etc). This should be contrasted against the majority of analytical techniques, which by design, are intended to be specific, if not for a single analyte then for a particular class of compounds. On the other hand, NMR is a multi-parametric, non-specific, means of detection that also provides a wealth of structural information.As such it can enable not only the detection of compounds present in a sample but also allow them to be identified. This feature of NMR as a bioanalytical technique allows the analyst to prospect for hitherto unexpec- ted markers of disease or toxicity, without first having to predict their likely outcome. Practical Considerations Apart from the problems associated with sensitivity, the most obvious practical difficulty in obtaining good quality NMR spectra of biological fluids is the suppression of the signal of the water protons, which would otherwise dominate the spec- trum.3 A number of solutions to the problem of suppression of the water signal have been described. These range in complex- ity from freeze drying the sample, followed by redissolution in 2H20, the application of a secondary irradiation field at the water resonance frequency, spectral selection based on TI relaxation time or approaches based on the augmentation of the water T2 relaxation time by chemical means.4 In the latter instance the water signal is subsequently attenuated using Carr-Purcell-Meiboom-Gill spin echo methods.These methods can be successfully employed to obtain NMR spectra of biological fluids without difficulty.1 Another important consideration is the nature of the biofluid, as each has its own distinct physico-chemical proper- ties that, at least in part, govern the type of NMR experiment to be employed for bioanalysis.1 However, the dynamic physico-chemical properties of biofluids are also of consider- able interest, particularly in multi-compartment fluids such as plasma and bile.Nuclear magnetic resonance spectroscopy is unique in its ability to probe such processes in intact biofluids and this might further aid the diagnostic potential of the technique.’ As an illustration of the type of data forthcoming from NMR spectroscopy a 600 MHz spectrum of human urine is shown in Fig. 1, from a normal healthy subject and a subject with asymptomatic 5-oxoprolinuria (a rare inborn error of metabol- ism). In addition to the large number of common resonances there are several significant novel resonances from the S-oxoprolinuric subject corresponding with the characteristic signals of S-oxoproline itself. The great utility of NMR of biofluids as a screening pool for inborn and acquired errors of metabolism is discussed below.The enormous complexity of the spectrum (there are normally >3000 resolved lines in the full spectral width, without resolution enhancement) is a measure of their biochemical information content. However, this very complexity can pose spectral assignment problems that require advanced multipulse and two-dimensional NMR methods for their solution.h In future, as higher field instrumentation becomes available even higher frequency measurements will prove useful in minimizing peak overlaps and will give more resolved resonances. Furthermore, the biochemical information density that is given by NMR spectro- scopy has led to the use of pattern recognition methods for data compression and biochemical classification (see below).Clinical Applications of 1H NMR Spectroscopy Proton NMR has found applications in various clinically important situations including: (i) screening and monitoring metabolic diseases such as diabetes mellitus or inborn errors of metabolism;3-7 (ii) investigations on the biochemical mechan-184 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 isms associated with disease processes and/or responses to drug therapy;3.8 and (iii) monitoring of patients following organ transplantation for evidence of organ rejection .g One of the most successful applications in the clinical use of NMR has been the detection of a wide range of inborn errors of metabolism in children. Although most of these diseases are, mercifully, rare, they can have severe consequences if a suitable treatment ( e .g . , modification of diet) is not provided rapidly. A feature of many of these inborn errors of metabol- ism is the high concentrations of unusual metabolites which are observed in the body fluids. These substances are readily detected by 1H NMR, with little or no sample preparation, permitting speedy diagnosis and 1H NMR is a useful alternative to conventional gas chromatography-mass spectrometry studies. Preatinine Glycine I \ 2 113 H 5-Oxoproline 1 P-Hydroxybutyrate Lactate Alanine \ trate I I I I 4 3 2 1 a/PPm Fig. 1 Aliphatic portions of a 600 MHz 1H NMR spectra of: (a) a subject with asymptomatic 5-oxoprolinuria; and (b) urine from a normal healthy subject Applications in Analytical Toxicology The applications of IH NMR in analytical toxicology may be divided into two broad areas: (i) the detection of deliberate or accidental drug overdose or exposure to noxious sub- stances;s.“) and (ii) the investigation of mechanisms of toxicity resulting from the administration of foreign compounds to man and animals.11.12 In cases of drug overdose, diagnosis and clinical decisions on appropriate therapy must be made rapidly.The speed with which such information can be provided by IH NMR has already been described and studies of this type have been performed on a subject suffering from paracetamol overdose. This investigation revealed highly abnormal plasma spectra, whilst analysis of the urine showed that the normal pattern of paracetamol metabolites was grossly disturbed.8 In experimental toxicology, NMR can be used to fingerprint rapidly biofluids such as urine.This fingerprint can then be compared with that of a control animal and differences sought, as changes in these endogenous metabolite patterns have been shown to provide information on the location and severity of toxic lesions, and also to provide information into the underlying biochemical mechanisms of toxicity. In this way a variety of new biochemical markers for different types of toxicity have been detected. Such markers include urinary lactic acid (acute proximal tubule damage), urinary taurine (liver damage) and urinary creatinine (testicular toxicity). 13-15 The metabolic information present in the IH NMR spectra obtained during such investigations is often complex. In order to obtain the maximum information from these studies Nicholson and co-workers have applied computer-based pat- tern recognition approaches to the analysis of the resulting spectra.*”*s Thus, it has proved to be possible to take into account a large number of parameters, and to use techniques such as non-linear mapping in order to classify the type of toxicity being observed.16 Future roles for 1H NMR in analytical toxicology will certainly include: (i) screening for abnormal metabolite patterns in biological fluids in both chronic and acute toxicity studies; (ii) a continued search for new markers, or combina- tions of markers, that can be used non-invasively to determine the site and mechanism of toxicity; and (iii) non-invasive detection of chronic effects resulting from exposure to foreign compounds.In all these areas NMR provides an analytical tool of great power, which actively complements conventional methodologies. Conclusions The study of the composition of biological fluids, and the way in which changes occur in response to disease or toxicity, is well suited to the particular properties of 1H NMR spectroscopy. The range of problems that can be addressed using this technique is enormous, and the number of applications reported in the literature is growing steadily. It would be surprising if, given the results obtained to date, 1H NMR spectroscopy of biological fluids did not become an essential technique for the clinical biochemist or analytical toxicologist. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 References Nicholson, J .K., and Wilson, I . D., Prog. Nucl. Magn. Reson. Spectrosc.. 1989. 21. 449. Nicholson, J . K., Buckingham, M. J., and Sadler, P. J . , Biochem. J., 1983, 211, 605. Nicholson, J . K., O’Flynn, M., Sadler, P. J., Macleod. A., Juul, S . M., and Sonksen, P. H., Biochem. J . , 1984, 217, 365. Connor, S. C., Everett, J . E., and Nicholson, J . K., Magn. Reson. Med., 1987. 4,461. Nicholson, J. K.. and Gartland. K. P. R., NMR Biomed., 1989, 2, 63. Bales, J. R.. Higharn, D. P., Howe, I., Nicholson. J . K.. and Sadler, P. J.. Clin. Chem. ( Winston-Salem), 1984. 30. 426. Iles, R., Hind, A. J.. and Chalmers, R. A., Clin. Chem. (Winston-Salem). 1985. 31, 1795. Bales, J. R . . Bell, J . D.. Nicholson, J . K . , Sadler, P. J . , Timbrell, J . A., Hughes, R. D., Bennett, P. N., and Williams, R., Magn.Reson. Med., 1988, 6, 301. Foxall. P. J . D., PhD Thesis. University of London, 1991. Foxall. P.. Bending, M.. Gartland, K. P. R.. and Nicholson, J . K., Hum. Toxicol., 1989.9, 491. Gartland, K. P. R.. Bonner, F., Timbrell, J . A . , and Nicholson, J. K.. Arch. Toxicol.. 1989. 63, 97. Gartland, K. P. R., Bonner, F., and Nicholson, J . K.. Arch. Toxicol., 1989, 64. 14. Gartland, K. P. R . , Bonner, F., and Nicholson, J . K., Mol. Pharmacol.. 1989.35, 242. Sanins, S. M., Tirnbrell, J . A.. Elcombc. C. R., and Nicholson, J . K., Arch. Toxicol., 1990, 64. 407. Nicholson, J . K., Higham. D. P.. Timbrell, J . A.. and Sadler. P. J., Mol. Pharmacol., 1989, 36, 398. Gray, J . . Nicholson. J. K., andTimbrell. J . A . . Arch. Toxicol.. 1990, 64, 443. Gartland, K.P. R., Sanins, S. M., Lindon, J. C., Beddell, C., Sweatman. B., and Nicholson, J. K., NMR Biomed.. 1990, 3, 166. Gartland. K. P. R., Beddell, C. R., Lindon, J . C., and Nicholson, J . K., J. Pharm. Biomed. Anal., 1990, 8, 963.ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 185 Enantiospecific Bioanalysis Andrew J. Hutt Chelsea Department of Pharmacy, King’s College London, Manresa Road, London SW3 6LX There is currently considerable interest in the pharmacody- namic and pharmacokinetic properties of the enantiomers of synthetic chiral drugs, most of which are marketed as racemic mixtures. I Although the differential pharmacodynamic activity of drug enantiomers has been known for a number of years, only recently has the significance of stereochemistry in drug disposition been realized and become an issue for both the regulatory authorities and pharmaceutical industry.This resurgence of interest in drug chirality has been stimulated, in part, by the recent rapid developments in analytical method- ology particularly in the area of chromatography, suitable for the determination of individual enantiomers in samples of biological origin. 1-1 Two chromatographic approaches are available for enantio- specific analysis: (1) the indirect approach, involving the formation of stable diastereoisomeric derivatives by reaction of the analyte(s) with a chiral derivatizing agent (CDA) followed by achiral chromatography; and (2) the direct approach, involving the formation of unstable or labile diastereoisomeric complexes by, for example, the use of a chiral stationary phase (CSP) or a chiral mobile phase additive (CMPA).Both of these approaches will be examined briefly below with an emphasis on their potential pitfalls and possible solutions to bioanalytical problems. Indirect Approach The formation of diastereoisomeric derivatives obviously requires the availability of an optically pure derivatizing agent and the presence of a suitable functional group on the analyte(s) which may undergo derivatization. Over the last few years several useful compilations of chiral reagents and derivatization methods have appeared.l.1.s The formation of covalent diastereoisomers may give rise to a number of problems associated with the enantiomeric purity of the derivatizing agent, racemization of the CDA during derivatization, low product yield and/or selective derivatiza- tion, i.e., is the measured ratio of diastereoisomers identical with the original enantiomeric ratio? Some CDAs, e.g., those based on L-proline, have achieved notoriety associated with lack of enantiomeric purity and stereochemical stability, e.g. , N-trifluoroacetyl-r--prolyl chloride.6 The potential problems associated with this class of reagent may be illustrated by the work of Adams et al. ,7 who attempted to develop a method for the determination of the enantiomers of ketamine using (S,S)-trifluoroacetylproline anhydride as a CDA. The derivati- zation reaction gave poor yields, was stereoselective and the CDA racemized. Differential detector responses may also be observed with diastereoisomeric derivatives. Lindner et a1.8 recently reported the chromatographic resolution of the enantiomers of the p-blocking drug propranolol using ( R , R)-diacetyltartaric anhy- dride as a CDA.On examination of the HPLC detector responses to equal amounts of the two diastereoisomeric ester derivatives, differences of 8 and 20% were observed in activity to UV and fluorescence detectors, respectively. The examples cited above illustrate the potential problems associated with this approach to enantiomeric analysis. The main advantages of the indirect methods are that careful choice of the CDA may well facilitate analysis by, for example, increasing the sensitivity of the analyte(s) to the detector system, and also that conventional highly efficient achiral chromatographic stationary phases may be used.It should not be forgotten that many metabolic processes, e.g., glucuronida- tion, result in the formation of diastereoisomeric metabolites which may be resolved using conventional chromatographic phases.4 Direct Approach Since the introduction of the first HPLC CSP in 1981, the number of commercially available columns has increased considerably, about 50 being currently available. Many of the constraints outlined above for CDAs are of much less importance if CSPs are used, e.g., the CSP need not be 100% enantiomerically pure for useful resolutions to be obtained, and should derivatization of the analyte(s) be required, then achiral reagents may be used. The CSPs may be divided into two main groups: 1. the designed CSPs where the mechanisms of resolution are fairly well understood and the elution order of a pair of enantiomers may be predicted, e.g., the Pirkle or brush phases; and 2.the empirical phases where the mechanisms of resolution are not well understood, resolution is dependent on a trial and error approach and rational prediction of elution order is not possible, e.g., the protein-based phases. The application of CSPs to bioanalytical work is fraught with chromatographic conditions tend to be fairly restricted and the presence of trace contaminants in samples of biological origin, e.g., trace solvent impurities, may have marked effects on both retention and enantiomeric resolution; ii. the choice of internal standards is more complex than in conventional chromatography; iii.the chromatographic efficiency of CSPs is often low, e.g. , the protein-based CSPs tend to have a low sample capacity which may limit the analytical sensitivity; iv. interference from the components of plasma may occur in the analysis and damage the CSP; v. coelution of drug enantiomers and those of a structurally similar metabolite may occur, e.g., the enantiomers of the non-steroidal anti-inflammatory agent pirprofen may be resolved using an (R)-N-(3 ,S-dinitrobenzoy1)phenylglycine phase, but the combined use of both the CSP and a CDA, (R)-1-phenylethylamine, was required in order to separate the resolved enantiomers of the drug from those of the metabolic oxidation product pirprofen ‘pyrrole’. 10 Simi- larly, the separation of the enantiomers of verapamil from those of norverapamil, the demethylated metabolite, using the protein-based CSPs is problematic.11 Some of the above problems with CSPs have been solved by the use of coupled column chromatography, the CSP following a conventional achiral stationary phase, the two columns being linked via a switching valve.Using this approach, the total drug present in a sample may be determined following elution from the achiral column, and the enantiomeric composition deter- mined following transfer of an appropriate fraction of the eluate to the CSP. Difficulties which may arise using this approach are associated with mobile phase compatibility between the two stationary phases. The shielded hydrophobic phases (Hisep, Pinkerton ISRP) utilize mobile phases which are compatible with the protein-based CSPs and the racemic forms of the designed phases may also be utilized in this approach (see Table 1). Additional complications involve the low column efficiency of the CSP, resulting in peak broadening with a consequent reduction in analytical sensitivity.This may problem^:^ i.186 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 Table 1 Bioanalytical applications of coupled column chromato- graphy Achiral phases* CSP" Application Reference Hisep a,-AGP Verapamil, norverapamil 11 Pinkerton (ISRP) BSA Warfarin 12 Nucleosil-phenyl B-CD Tcrbutalinet 9 Pinkerton (ISRP) aI -AGP Warfarin 13 ( R , S)-Naphthylalanine OD Ifosfamide, Cyclophosphamide 14 * al-AGP, a,-acid glycoprotein-bonded CSP; BSA, bovine serum albumin-bonded CSP; p-CD, P-cyclodextrin-bonded CSP; OD, cellu- lose tris(3,S-dimethylphenylcarbamate)-bonded CSP; ISRP, internal surface reversed phase.t Peak compression and reduction in band broadening achieved by use of a stronger eluent, 0.05 mol dm-3 ammonium acetate (pH 6), for the CSP compared with 0.01 mol dm-3 (pH 4) for the achiral phasc. be overcome by alteration of the mobile phase composition between the achiral and chiral phases, e.g., terbutaline (Table 1); also, it has been suggested that the column order could be reversed, i.e., with the CSP before the achiral phase.15 Sample Manipulation Enantiomeric analysis frequently involves a considerable number of sample clean-up procedures prior to the final determination. Such manipulations may give rise to a number of problems. In a study16 concerned with the determination of the enantiomeric composition of mexiletine in plasma, it was found that both drug recovery and enantiomeric composition were influenced by the reagents used to precipitate plasma proteins.Thus the use of sodium hydroxide resulted in a low recovery of (R)-mexiletine compared with the S-enantiomer, the original enantiomeric composition of the sample being restored when a mixture of zinc sulphate and barium hydroxide was used for protein precipitation.16 Problems of greater complexity to deal with are those associated with non-chiral differentiation. It is generally assumed that achiral processes, e.g., achiral chromatography, will not result in changes in the enantiomeric composition of a non-racemic mixture of isomers. However, several papers have appeared that indicate that such assumptions may not always be valid.17-19 Non-chiral differentiation results in the progres- sive enrichment of the enantiomer that is present in excess. It is thought that such effects are due to molecular association between enantiomers via hydrogen bonding and/or van der Waals interactions and may also be concentration dependent. Such effects have also been observed in NMR spectroscopy and polarimetry, i.e., the observed optical rotation of a mixture of enantiomers was not directly related to isomeric composi- tion.20 As the majority of samples of biological origin will contain non-racemic mixtures of enantiomers, it is important that appropriate analytical validation is carried out to ensure that non-chiral differentiation docs not add to the complexity of the analysis.Conclusion The determination of drugs in biological fluids is one of the most difficult areas of analytical chemistry, involving the determination of low concentrations of analyte in highly complex media. To add to this the problem of enantiomeric differentiation moves the area into a new level of complexity. There are a variety of methodologies available for enantio- specific bioanalysis, all of which have possible advantages and limitations, and no single method may be considered appro- priate for every compound or for all possible applications. The problems associated with enantiomeric bioanalysis are many and the effective use of the modern methods requires an appreciation of the potential sources of error involved.1 2 3 4 5 6 7 8 9 10 11 12 13 14 1s 16 17 18 19 20 References Ariens. E. J., Wuis, E. W.. and Veringa, E. J., Biochem. Pharmacol.. 1988. 37. 9. Testa, B., Xenobiofica. 1986, 16, 265. Drug Stereochemistry. Analytical Methods and Pharmacology, eds. Wainer, I. W.. and Drayer, D. E., Marcel Dckker, New York, 1988, p. 1. Hutt, A. J.. Prog. Drug Metah.. 1990, 12, 257. Gal, J., LC-GC, 1987, 5, 106. Silber, B., and Riegelman, S . . J . Pharmacol. Exp. Ther.. 1980, 215, 643. Adams, J. D.. Woolf, T. E., Trevor. A. J., Williams, L. R., and Castagnoli, N., J . Pharm. Sci., 1982, 71, 658. Lindner, W., Rath, M., Stoschitzky, K., and Uray, G., J . Chromatogr., 1989, 487, 375. Edholm. L.-E., Lindbcrg, C., Paulson, J . , and Walhagen, A., J.Chromatogr.. 1988,424, 61. Sioufi, A., Colussi, D., Marfil, F . , and Dubois, J. P., J. Chromatogr., 1987, 414, 131. Chu. Y.-Q., and Wainer, 1. W., J . Chromatogr., 1989,497.191. Chu, Y.-Q., and Wainer, I . W.. Pharm. Res., 1988, 5 , 680. McAleer, S. D., and Chrystyn, H., J. Pharm. Pharmacol., 1990.42.21P. Masurel, D., and Waincr, I. W.. J. Chromatogr., 1989, 490, 133. Walhagen, A., Edholm. L.-E., Hecremans. C. E. M . . van der Hoeven, R. A. M.. Niessen. W. M. A . , T,jaden, U. R.. and van der Greef, J., J . Chromatogr.. 1989,474, 257. McErlane. K. M., Igwemezie. L., and Kerr, C. R.. J . Chromatogr., 1987,415, 335. Cundy, K. C., and Crooks, P. A., J . Chromatogr.. 1983, 281, 17. Tsai. W.-L., Hermann, K., Hug, E., Rohde. B., and Dreiding, A. S . , Helv. Chim. Acta, 1985.68, 2238. Matusch, R., and Coors, C.. Angew. Chem. Int. Ed., Engl., 1989, 28, 626. Horeau, A., Tetrahedron Lett., 1969, 3121. Supercritical Fluid Chromatography of Polar Compounds E. David Morgan, Huiping Huang and Ian D. Wilson Department of Chemistry, University of Keele, Staffordshire ST5 5BG The advantages of a supercritical fluid as a moving phase in chromatography have been grasped and applied in a number of areas in recent years, so that supercritical fluid chromato- graphy (SFC) is now an active area of research. It has not yet been readily accepted as a routine method of analysis, perhaps because of a reluctance to accept that SFC can perform either more quickly or with advantage, separations and analyses that appear to be achievable with existing GC or HPLC methods.We think this view is mistaken, and illustrate the unique advantages of SFC with some examples from our own work. Relatively non-polar compounds have been intensively studied using supercritical CO2 as the mobile phase in modified gas chromatography equipment. This type of system has the advantages of maximum resolution and the use of the sensitive and universal flame-ionization detector, but has the disadvan- tage of the low polarity of the mobile phase. In order toANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 187 chromatograph more polar compounds, a mixed mobile phase, high-performance liquid chromatography (HPLC) technology and ultraviolet detection are required. With such a system, organic compounds of high polarity can be chromatographed quickly with high sensitivity and resolution, using a super- critical mobile phase.Experimental The apparatus used in this work is essentially the supercritical fluid chromatograph (LDC Analytical, Stone, Staffordshire) as supplied. The only additional component is a cylinder of CO? provided with a dip tube to permit the removal of liquid CO?. Cooled CO? and methanol are pumped (controlled by a programmer), mixed and passed through a pressure dampener, to remove baseline noise at high sensitivity, into an oven to bring the mixture of C02 and methanol above the supercritical point. The oven also houses an HPLC injection valve, a precolumn, an analytical column (aminopropyl silica 150 x 4.6 mm i.d. for much of this work) and a pressure regulator valve. The mobile phase passes from the analytical column, out of the oven to the detector and back to the pressure regulator in the oven.The depressurized effluent is bubbled through water. Further details can be found elsewhere.'-3 In general, a pressure of 3000 psi (20.7 MPa), temperature of 55"C, flow rate of from 1 to 4 ml min-l and from 5 to 20% methanol in CO? as the mobile phase were used, unless otherwise stated. Strictly, some of the separations carried out with high proportions of methanol were subcritical at the temperature used. : COOCH3 CH300C- '- 0 (11) has considerable potential as a natural insecticide and plant protectant. Azadiractin is a highly polar substance, and is obtained from Neem seeds as a crude extract contaminated by large amounts of less polar compounds.Reversed-phase HPLC is therefore not appropriate. HPLC on silica is slow, and unsuitable for solvent programming. Azadiractin can, however, be determined by SFC with high sensitivity and in a very short period of time in the presence of fairly large amounts of non-polar contaminants.3 Hence SFC could, with certain advantages, be used as a standard method for determining the potency and value of crude Neem extracts in commerce. Here too, combination of SFE for extraction and SFC for quantifica- tion would present a powerful and labour-saving analytical method. Acidic Drugs Anti-inflammatory drugs of the ibuprofen (111) and naproxen (IV) type are strongly acidic, and therefore not readily Ecdysteroids The ecdysteroids [insect moulting hormones, see (I)] are a group of polyhydroxylated sterols having a cholestane skeleton and all possessing a 7-en-6-one ultraviolet (UV) chromophore (A,,, = 242 nm).l The identification and quantification of OH \ OH 0 (1) these substances are important to a large group of biochemists and physiologists.At present, HPLC is used for their analysis, but this method lacks the sensitivity desirable for insect work. That the separation of ecdysteroids can be achieved much more rapidly by SFC than by HPLC with comparable resolution has been demonstrated, but more importantly, SFC provides higher sensitivity,z in an area where even a 10-fold increase in sensitivity can provide a great advantage in the amount of insect material required. I n order to complete this work, a method is now required to enable supercritical fluid extraction (SFE) of the ecdysteroids directly from the insect, so that it can be combined with the SFC method for quantification and identification.This could eliminate the lengthy isolation procedures now employed. If such a method can be perfected, the great advantages of supercritical fluid methods will be fully displayed. Azadiractin Azadiractin (11) is a complex triterpenoid-derived substance from the seeds of the Neem tree (Azadiractin indica), which (IV) chromatographed in capillary gas chromatography (GC) condi- tions without derivatization. High-performance liquid chro- matographic methods require acidification of the mobile phase to obtain ion-suppression. They can easily be chromato- graphed on aminopropyl silica under supercritical conditions, retaining good peak shape.4 With SFC, such drugs can easily be determined with little preparatory clean-up.This is illustrated by SFC of solid-phase extracts of human urine and urine to which three such drugs had been added. The three drugs were readily separated, quickly eluted and the peaks were free of interfering substances, using 20% methanol in C02 as the mobile phase.-' No addition of an acidic modifier to the mobile phase was necessary. Basic Drugs Basic drugs are often troublesome on either GC or HPLC because of their strong interaction with the stationary phase and its support. Either they must be derivatized first, or special phases and conditions must be employed for their chromato- graphy. Under SFC conditions, however, they can be chro- matographed normally.This has been shown by the SFC of a range of @-blockers using 10% methanol in C02, by which they were eluted with symmetrical peak shapes from an amino-188 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 propyl column.4 These compounds were not eluted from a cyanopropyl column by the supercritical C02-methanol mix- ture, but after the addition of 0.4% of triethylamine to the methanol, elution from this phase was also possible.4 Mass Spectrometry While linked techniques are readily achieved with GC [for example, GC-MS (mass spectrometry) and GC-FTIR (Fourier transform infrared spectroscopy) are now routine], the problems of eliminating the mobile phase to carry out MS with HPLC have not yet been fully solved. Supercritical fluid chromatography provides much less of a problem, and SFC and MS have been much more readily brought together.sJj While true electron impact type mass spectra are obtained with C 0 2 alone, as mobile phase, the spectra move towards chemical ionization type with increasing amounts of added methanol .? More fragmentation information can be obtained by raising the temperature of the source, as illustrated for the several examples of the ecdysteroids ,2 where mass spectra are particu- larly important for identification.It should be noted that as an alternative to the sensitive UV detection, there is a light scattering total mass detector available for non-absorbing entities and in-line radiocounting is also practical for labelled compounds. As little as 10000 counts min-1 of [ “C]-labelled compound can be detected in a radio-flow cell .7 We thank the staff of LDC Analytical for help and guidance on numerous occasions, and Professor D.E. Games for the SFC mass spectra. H. P. H. thanks the Committee of Vice- Chancellors and Principals (CVCP) for the award of an Overseas Research Studen tship. References Morgan, E. D., Murphy, S. J . , Games. D. E., and Mylchreest, I . C., J . Chromatogr.. 1988, 441, 16.5. Raynor, M. W.. Kithinji, J . P., Bartle. K . D., Games, D. E.. Mylchreest. I. C., Lafont, R.. Morgan, E. D., and Wilson, 1. D., J. Chromatogr.. 1989, 467, 292. Huang, H. P . , and Morgan. E. D., J . Chromatogr.. 1990. 519, 137. Methodological Surveys in Biochemistry Analysis, eds. Roberts. D. W., Wilson. I . D., and Reid, E., The Royal Society of Chemistry, London. 1990, vol. 20. p. 2.57. Wright, B. W., Kalinoski. H. T., Udseth, H. R., and Smith, R. D.. J . High Resolut. Chromatogr. Chromatogr. Cornmun., 1986, 9, 145. Games. D. E., Berry, A. J., Mylchreest, 1. C., Perkins, J. R., and Pleasance, S., Eur. Chromatogr. News, 1987, 1, 10. Ruane, R. J . , Tomkinson, G . P., and Wilson, I. D. J. Pharm. Biomed. Anal., 1990, 8, 1091. Nuclear Magnetic Resonance Vol20 Senior Reporter: G. A. Webb, University of Surrey Series: Specialist Periodical Reports Nuclear Magnetic Resonance Vol. 20 reviews the literature published between June 1989 and May 1990. Contents: N.M.R. Books and Wiews, Theoretical and Physical Aspects of Nuclear Shielding, Applications of Nuclear Shielding, Theoretical Aspects of Spin-Spin Couplings, Applications of Spin-Spin Couplings, Nuclear Spin Relaxation in Liquids and Gases, Solid State N.M.R., Multiple Pulse N.M.R., Natural Macromolecules, Synthetic Macromolecules, Conformational Analysis, Nuclear Magnetic Resonance of Living Systems, Nuclear Magnetic Resonance Imaging of Living Systems, N.M.R. of Paramagnetic Species, N.M.R. of Liquid Crystals and Micellar Solutions, Author Index. Hardcover xxii + 602 pages 216 x 138 mm Price f140.00 ISBN 0 851 86 432 5 April 1991 Electron Spin Resonance Vol 12B Senior Reporter: M.C.R. Symons, University of Leicester Series: Specialist Periodical Reports This latest volume contains critical reviews of developments during mid 1989 - mid 1990 in the field of inorganic and bio-inorganic aspects of electron spin resonance. Brief con tents: Transition Metal Ions, Laser Magnetic Resonance Spectroscopy, ESR of Transition Metal Ions in Zeolites, Metalloproteins, EPR Imaging, Inorganic and Organometallic Radicals, Author Index. Hardcover xiv + 258 pages 216 x 138 mm Price f 105.00 ISBN 0 85186 891 6 April 1991 I I ROYAL S O , - ~ ~ T ~ OF CHEMISTRY 6s Information Services To Order, Please write to the: Royal Society of Chemistry, Turpin Transactions Ltd, Blackhorse Road, Letchworth, Herts SG6 1 HN, UK. or telephone (0462) 672555 quoting your credit card details. We can now accept AccessNisa/MasterCard/Eurocard. Turpin Transactions Ltd, distributors, is wholly owned by the Royal Society of Chemistry. For information on other books and journals, please write to: Royal Society of Chemistry, Sales and Promotion Department, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK. RSC Members should obtain members prices and order from : The Membership Affairs Department at the Cambridge address above.

ISSN:0144-557X    

DOI:10.1039/AP9912800177

出版商:RSC    

年代:1991

数据来源: RSC

摘要:

ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 189 Teaching of Modern Analytical Chemistry- Fitting the Skills The following are summaries of four of the papers presented at a Meeting of the Analytical Division held on November 26th' 1990, in the Scientific Societies' Lecture Theatre, London w1. The Aims of Teaching Analytical Science in Higher Education F. W. Fifield School of Applied Chemistry, Kingston Po I ytechnic, The need for teaching analytical science in modern society is indisputable. Industry, commerce, environmental monitoring, law enforcement, medicine and other areas utilize analytical science to a substantial extent. This in turn generates demands for properly educated analytical scientists. Hence there are demands to educate for a general appreciation of analytical science and its function and also more specifically to produce suitably qualified analytical scientists.A pattern of courses demanding analytical science inputs has grown to satisfy society's needs for qualified people. Some of these courses, e.g., MSc, short courses and a limited number of undergraduate courses, are aimed at producing specialist analytical scientists. Others, such as mainstream chemistry courses, need analytical science to underpin the understanding of the main subject and to provide a qualification with a suitable vocational balance. A further group such as the earth sciences and life sciences need a knowledge of some aspects of analytical science. Resources available always present problems. Equipment must be up-to-datc, reflecting what is in use in industry but must nevertheless be suited to demonstrating fundamental Penrh yn Road, Kingston upon Thames KTI 2EE principles.With regard to staff it is usually possible to find people to teach specific areas of methodology, but much more difficult to do so when the teaching of some of the broader aspects of the subject is required, e.g. , the context and function in society or data interpretation. In setting the teaching aims, consultation with employers and users of analytical science is of the greatest importance. The input can be by formal consultation in advisory groups or surveys. Often, however, the most valuable ideas come from informal contacts during consultancy, joint research or sand- wich course visits. My aims in teaching analytical science would be to communi- cate an understanding of its context and function, data assessment and interpretation, selected methodology, practical skills and problem-solving skills.The balance would clearly depend on the over-all aims of the course. Communication skills are also frequently mentioned as a common weakness, and perhaps these should be added to the list. In order to achieve these aims it will be necessary to use a range of teaching methods such as lectures, tutorials, seminars, supervised practical work , projects and independent learning. Computer-assisted Learning of Analytical Chemistry John Boother Autoscribe Limited, 7 Hawkes Close, Wokingham, Berkshire RGI I 2SZ The presentation concentrated on the options open for further training of current employees within an organization with particular reference to computer-based training.The options were defined as off-site training (courses organized by colleges and instrument manufacturers), on-site training (visiting teachers) and training materials (distance learning). The subject of training materials was reviewed, covering books, audio tapes, audio-slide courses, video courses and computer-based training (CBT). Various aspects of CBT were discussed, including the use of expert systems, the interactive nature of CBT, and its advantages and the need for trainee assessments. Several examples were given from existing software packages emphas- izing ease of use, trainee interaction, knowledge bases and instrument simulation, e.g., HPLC. Multimedia, and the development costs of programmes, were mentioned together with a brief look at future needs as a conclusion.190 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 Analytical Short Courses for Industrial Needs Roger M.Smith Department o f Chemistry! L oug h bo ro ug h University of Tech no logy! L oug h bo roug h, L ekes te rs h ire LEI 7 3TU When industry comes on to the job market looking for new graduates, they often have an idealized model of the potential students that they seek from universities and polytechnics. Each individual sector of the chemical industry expects to find bright, highly motivated graduates possessing just the special- ized blend of skills and knowledge to slot into their closely defined position. This is probably as true of posts for analytical chemists as for organic synthetic, silicone or even uranium chemists.The potential employer would also like the graduates to have a broad knowledge of general chemistry, to be familiar with modern instrumentation, to have man-management skills, a detailed knowledge of COSHH, I S 0 9000 and GLP and preferably 3-4 years of previous industrial experience. For these graduates they often offer the prospects of routine work, low pay relative to the glamour professions of accountancy and related areas in the City and limited prospects for advancement and promotion. Then they wonder why recruitment is so hard. The reality is that today’s and tomorrow’s graduates will come in all shapes, sizes and skills, and will often have only limited industrial experience, particularly those from univer- sities as only a few offer sandwich courses.They will have limited experience of the state-of-the-art instrumentation, because it is too expensive and complex for teaching and its operation usually requires a long and dedicated learning process. Students cannot just learn about NMR spectroscopy or HPLC, they must also learn many other skills and about many other topics within a limited time span. Recent changes in practical work in schools mean that frequently formal techniques and manipulative skills are not encountered until tertiary education. However, these modern graduates will have been trained to a higher level than ever before simply because the subject of chemistry is itself expanding at a rapid rate. In analytical chemistry alone, the last 10 years have seen HPLC, microcom- puters, inductively coupled plasma spectroscopy, chiral separa- tions and many other topics come from research novelties to be a major part of the work of many laboratories and thus to be an additional essential part of the curriculum. The new graduates should all have a basic chemical knowledge, learning skills and an interest in new areas, some project experience and computer skills.Time does not permit tertiary education to provide a specialized training to any individual graduate to satisfy the particular needs of one employer. In any event, employers’ needs change rapidly and each different company would require different specializations. It is therefore for the employer to draw on the attributes of the graduates and indeed of all new employees and enable them to gain the necessary additional skills and knowledge for the specialized areas of their work.To develop the full potential of the new employee, the company therefore needs to plan a programme of in-service training which will expand into a continuous process of education throughout their careers. This can take many routes, in which external or internal short courses will play a major role. Short courses can be defined in many ways but are usually thought of as running for a limited span of 1 day to 6 months without resulting in a formal qualification, although sometimes they can form part of course for a qualification such as a part-time MSc. They can provide training for a new employee (and more experienced employees) in general areas, including personnel and project management, report presentation and communication skills, health and safety and so on.Within the analytical laboratory, short courses can also usefully build on a general chemical education to provide specialized skills. Courses that provide training in the use of particular instru- ments or data systems are usually provided by the manufac- turer or supplier and are dedicated to a particular system. Alternatively, the employee can be provided with technique- oriented courses, covering a specific area such as HPLC, immunoassays, Fourier transform IR interpretation or many others which would be directly related to their laboratory needs. Typically these courses are offered by specialized training organizations or individuals, academic institutions, universities, polytechnics and colleges and by professional societies such as the Royal Society of Chemistry and topic groups such as the Chromatographic Society, UV Discussion Group and trade affiliations.In addition to the needs of the new employee, companies are often in a state of flux or reorganization as requirements and priorities change and short courses can provide retraining for more established employees in new skills and responsibilities. Research and manufacturing companies may consider that they have all the necessary expertise themselves and could run their own courses using in-house experts. However, although this is necessary when specific company procedures or practices are involved, this approach has disadvantages.Not least it fosters the ‘not invented here’ syndrome and thus insulates the company from new and possibly different ideas. More import- ant, it is expensive and inefficient because the local experts will need to be taken off their normal duties for a significant time to prepare, organize and present the course, and this will usually be on a one-off basis for a small number of participants. In contrast, the external course organizers will usually run a course many times, often in conjunction with other related teaching, so audiovisual aids and lecture notes are already available and the lecturer is experienced in presenting the material. If the company has a sufficient number of potential participants and only limited practical work is required, a short course can be given at the place of work, but going away from the company site has many advantages.Separating the participants from their normal work environment means that they can concentrate on learning and are not continually disturbed by phone calls or demands for ‘urgent’ work or to solve ‘immediate’ problems. More important, it enables the participants to mix socially with other analytical chemists with similar interests from other companies and often with applica- tions chemists from suppliers of equipment who are participat- ing in the course as lecturers or demonstrators. These shared experiences can be very valuable and the informal seminars late at night in the bar or coffee room can often supply as much understanding as those formal lecture sessions which had occupied the days.At Loughborough University we have had a long and extensive experience in providing short courses in analytical chemistry for industry. We run 10-12 courses each year, which are attended by 30&350 participants mainly from the UK but also from Europe and occasionally from further afield. Many of the courses are well established and have been running annually for up to 15 years. The profile and content of the courses are continually changing and recent years have seen the provision of new courses on sensors, microbiological methods and supercritical fluid chromatography. Other courses have been updated as techniques change so that a course on separation methods for biochemical and biotechnology now contains a significant HPLC component that has replaced theANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 191 gel filtration methods popular only a few years ago.These changes are enhanced by close co-operation with the analytical instrument manufacturers who loan examples of the current models of instrumentation for hands-on use by the course participants. The Department also provides similar courses on-site for companies which have large numbers of potential participants. As a University, Loughborough has a tradition of industrial contacts through short courses and many are run in other departments of the University and by the Centre for Extension Studies. These can also include areas of interest in the chemical laboratory such as process-scale chromatography, health and safety and particle size characterization. This activity will shortly be reflected by the opening in 1991 of a purpose-built accommodation and lecture room facility for short courses.The reasons for running the analytical courses at Lough- borough, which are in addition to normal teaching and research activities, are to promote analytical chemistry and to increase industrial contacts which can be used to support undergraduate and postgraduate teaching and research. The courses must be self-funded and any profits provide a flexible source of finance which can be used to support the research activities of the Department, such as allowing conference attendance by staff and research students and the purchase of equipment that would not be possible from normal funds. In running the courses the aim is to give the participants an enhanced knowledge of the subject area, to introduce them to new skills and equipment and to provide a forum for discussion and advice, increasing their circle of contacts in the subject area.The typical participant is 20-30 years old, usually a relatively new employee with less than 1 year’s experience with the technique, although each course usually also attracts a sprinkling of older participants who are changing work areas or responsibilities. Overall, about 15% of the participants have never used the technique before attending the course. The participants are usually sent on the courses to enhance the background knowledge of their present work and to broaden their understanding of the potential of the technique.Some- times participants are sent to gain experience of new equip- ment so they can advise on purchase or from smaller companies so they can hopefully become ‘instant experts’ and set up and operate a new system that has just been delivered. Short courses have also played an important role in rapidly disseminating new techniques and ideas. Unlike exhibitions or scientific meetings, those participants on these courses who are usually older ‘decision makers’ within the company can see a range of the equipment in operation, try real samples or their own products and receive lectures from a range of experts and companies. Typical courses of this type have included the supercritical fluid chromatography courses at Loughborough, capillary zone electrophoresis at York and chiral chromato- graphy at Bradford.Short courses in analytical chemistry therefore provide a vital role in the on-going process of lifelong training and education which is the basis of a professional career in chemistry. Continuing Professional Development for Analytical Chemists Norma Chadwick Thames Polytechnic, London SE9 2HB This meeting offered an opportunity to present current ideas on continuing professional development both of direct rel- evance to analytical chemists and of more general interest. In introducing several topics it was hoped that interest would be generated as a basis for future discussion. A working party in analytical chemistry’ contained in its recommendations to higher education the request to expand postgraduate specialist short courses and updating provision relevant to analytical chemistry.The on-going professional development needs of analytical chemists are considerably wider than analytical chemistry itself. Technical Updating There is obviously the need to keep up to date in technical subjects. Short courses are a major way in which this requirement is met. Higher education establishments inter- ested in developing short courses can gain help and advice from a number of sources. (i) The Society’s Post-experience Course Committee will often share the work and risk in presenting new subjects as short residential courses; (ii) funding through the Professional, Industrial and Commercial Update (PICKUP) scheme provides pump priming money for course develop- ment; (iii) open learning materials are available in order to enable a concentration of the short residential parts of the courses on practical skills and giving participants freedom to learn theory and interpretative aspects at a rate appropriate to their ability and available time; (iv) credit accumulation awards in continuing education are available through the Business and Technician Education Council (BTEC), enabling successful participants in short courses to demonstrate competence when applying for Licentiate of the Society or to gain credit towards a Council for National Academic Awards (CNAA) degree or masters degree. Management Skills Career progression requires management skills development at a number of levels-organizational and interpersonal, in- formation technology and quality assurance.Any analytical chemist’s promotion away from the bench requires a wider knowledge of business and management but it does not dispense with the need to keep technically up to date. Postgraduate opportunities for study are now including the concept of ‘Professional Masters Programmes’, providing by credit accumulation the facility for an individual to identify hidher own programme of study and to relate that programme to personal career requirements. Such a masters award might contain elements of a technical nature, management skills and a major investigative project. Fig. 1 shows an example of a structure for a professional masters award. Co m pu I so ry (40 credits) tA 0 Management element (40 credits) 4- .- - 2 ---- f Technical element learning (40 credits) Maximum 60 credits, no more than 30 in either element Example of a structure for a professional masters award Fig.1192 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 A major feature of credit based study is the incentive to progress by acknowledging recent relevant study and in- company or experiential learning. Returning From a Career Break A large number of women chemists leave the profession each year, mainly for domestic reasons. Few return. This must be seen as a serious waste of education and training. Membership figures, Table 1, showing the proportion of women in chemistry at ‘A’ level entry and in Royal Society of Chemistry membership in 1989, provides a startling demonstration of the failure of women to develop in the profession. Table 1 Proportion of women in chemistry at ‘A’ level entry and in RSC membership, 1989 Male Female F: M (%) ‘A’ Level so RSC Membership- Student 2700 1391 34 Graduate 3549 1168 25 Member 13294 1159 9 Fellow 7 254 124 1.7 Trend in female membership (%)- 1987 1988 1989 9.7 10.2 10.6 The proportion of women reaching Fellowship status in the RSC is the lowest in any membership figures from a profes- sional body encountered so far by this writer.In an employ- ment situation where fewer young people are choosing to follow science as a career, it makes clear sense to provide an accessible route back into the profession for women returners, i.e., people who have already demonstrated a scientific interest and ability. The provision of courses aimed at updating returners and provided at convenient times and places is much needed.A successful course operates at the Robert Gordon Institute in Aberdeen and a number of other institutions in other parts of the UK have plans aimed at awarding the Certificate of Applied Chemistry to successful applicants, thus offering a route to LRSC. Undoubtedly, a major difficulty is in financing this type of course, and Government or EEC money must be sought . Men Women Fig. 2 Economically activc adults reporting training for current job, 1987 However, even in employment there is a need to ensure that all training opportunities are equally accessible to men and women. Government data2 (Fig. 2) show that fewer women than men undergo training at work. Does this reflect reluctance to progress or a bias in provision? Professional Recognition The Indicative Register of Analytical Chemists will in January 1991 become the fourth such register provided by the RSC. The need for a register is well documented elsewhere and it will provide an excellent vehicle for ensuring professional develop- ment. How will higher education contribute to the on-going training requirements of prospective members of the register? For the credibility of their role in the educating and training of analytical chemists, it is essential that this future development is squarely addressed by higher education both for the development of the teaching staff themselves and for the maintenance of academic standards in the courses provided. In summary, the continuing professional development of an analytical chemist can be seen as stretching almost from cradle to grave with differing emphases along the way. Higher Education must be flexible and willing to meet these needs. References The Royal Society of Chemistry Analytical Division Working Party on The Future of Analytical Chemistry. Anal. Proc., 1990, 27, 166. Training Statistics 1990, report published by the Government Statistical Service, HM Stationery Office, London. 1990.

ISSN:0144-557X    

DOI:10.1039/AP9912800189

出版商:RSC    

年代:1991

数据来源: RSC

摘要:

ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 193 Research and Development Topics in Analytical Chemistry The following are summaries of three of the papers and posters presented at a Meeting of the Analytical Division held on March 21st-22nd, 1989, in the National Institute of Higher Education, Dublin. Summaries of thirty other papers and posters presented at the Meeting were published in the October and November, 1989, issues of Analytical Proceedings. Applications of a Slotted Tube Atom Trap and Flame Atomic Absorption Spectrometry: Determination of Antimony in Copper-based Alloys After Hydride Generation Michael Harriott, D. Thorburn Burns and Narong Chimpalee Department of Analytical Chemistry, The Queen's University of Belfast, Belfast BT9 5AG Chemical generation of volatile hydrides with subsequent atomization offers sensitivity greatly superior to that obtained with conventional flame atomic absorption.1 Antimony is one of the elements that forms a suitable hydride, stibine (SbH3). The use of a slotted quartz tube through which the flame passes to increase sensitivity has been reported using nebulized solutions.?-4 This technique coupled with hydride generation has been examined for the determination of Sb in copper-based alloys. Experimental Instrumentation A Perkin-Elmer Model 403 atomic absorption spectrometer equipped with a Perkin-Elmer Model 56 chart recorder set at the 10 mV range was used. The spectrometer conditions for Sb were: wavelength, 231.5 nm; lamp current, 14 mA; flame, lean air-acetylene; aspiration rate, 5.9 ml min-1; and bandpass, 0.7 nm.The hydride generation system is shown schematically in Fig. 1. The slotted tube atom trap (STAT) was made from satin surface transparent quartz from Thermal Syndicate. Tube dimensions were 115 x 3 mm entrance slot with a row of six holes, 6 mm diameter, 9 mm apart for exit at 180" to entrance slot.4 A cradle system similar to that of Brown and Taylor3 was constructed to align the slotted tube directly above the burner head slot along the optical path of the spectrometer. The cradle was attached to the burner head using the two burner safety wire retention screws, and the slotted tube was held in place by two V-shaped adjustable plates on the loading arm by springs (8.00 mm gap between the burner head and the bottom of the slotted tube).The design allows a change-over from analysis with the STAT to a conventional flame in seconds.4 Pressure-release system To nebulizer S of the AAS instrument To waste Fig. 1 Schematic diagram of the hydride generation system Reagents and Solutions Antimony(n1) stock solution, 1000 pg ml-1 of Sb aspotassium antimony tartrate (SpectrosoL, BDH). Antimony(v) stock solution, 1000 pg ml-1. Dissolve 0.1 g of Sb metal (99.9999% Sb shot, 0.1 mm; Johnson Matthey) in 10 ml of concentrated hydrochloric acid and 2 ml of nitric acid and dilute with de-ionized water in a 100 ml calibrated flask. Sodium tetrahydroborate(1rr) solution, 2% mlv. Dissolve 2 g of NaBH4 (98% ; Aldrich) in 100 ml of de-ionized water; after stabilizing with sodium hydroxide (one pellet), the solution is filtered through a Whatman No.540 filter-paper. All other reagents were of analytical-reagent grade, and doubly purified water [distillation followed by de-ionization (Egla C114)] was used throughout. Hydride Generation Procedure Transfer by pipette 2 ml of the sample solution (containing 3% vlv hydrochloric acid) into the generation flask. Adjust the volume of the solution in the generation flask to 7 ml with distilled water. Turn the three-way stopcock to connect the generation flask with the nebulizer (N2 flow rate = 800 ml min-1). Inject 3 ml of 2% mlv NaBH4 solution and record the absorption signal. Finally, turn the three-way stopcock to aspirate water into the flame. Drain and wash out the generation flask prior to addition of the next sample.Oxidation State Study The hydride absorption signals from 1 pg ml-1 of Sb"1 and SbV were compared. The results showed that the absorption signal from SbV was about 75% lower than that from SbIIl. As the Sb in the sample solutions of copper-based alloys is in the form of SbV, it must be reduced to Sb"1 in order to increase sensitivity. Sodium sulphite has been found to be a satisfactory reducing agent for SbV in the presence of copper ions and hydrochloric acid.5 The absorption signals must be recorded within 2 h of final sample preparation.1.6 Interference Study An interference study was carried out by using 0.4 pg ml-1 of Sb"1 for the elements and concentration ranges in excess of those expected in copper-based alloys. The results are sum- marized in Table 1.Procedure for Copper-based Alloys Weigh the sample (to contain about 0.1 mg of Sb) into a 150 ml194 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 Table 1 Effect of foreign ions Ratio of ion Change in Ion to Sb"1 peak height (Yo) C U " 125 -20 - 25 2500" - Pb" 1250 - 12.5 1250* - ZnI1 1250 - FeI" 1250 - 100 1250t - MnI1 250 - Nil1 12.5 - 25 250 - 100 250* - SnIV 250 - Al"' 250 -9.0 250" - CO" 250 - 28 250* - BiIII 150 -55 150" - SiIV 250 - AslII, SeIV - Ag' 25 * Add 1 ml of 1.10-phenanthr~line~ and 4 ml of 2% thiourea.% t Add 0.5 g of sodium sulphite.5 prepared by using standard SbV solutions with added copper ions and proceeding as for the copper-based alloy samples. Results and Discussion All samples were analysed using a conventional flame and with STAT for comparison purposes.The results obtained (Table 2) for the determination of Sb in a range of copper-based alloys were in good agreement with the certificate values. For 0.4 pg ml-' of Sb"1, the relative standard deviations were 5.18 and 1.27% for the conventional flame and STAT method, respectively. The main advantages of STAT over the conventional flame method are increased sensitivity (enhancement factor = 1.8) and in the precision attainable. Table 2 Determination of Sb via SbH3 in copper-based alloys Found (YO m/m)* Certified value STAT Flame Sample (YO m/m) BCS-CRM 207/1 0.080 0.084 k 0.002 0.085 + 0.001 BCS-CRM 364 0.18 0.196 & 0.005 0.184 f 0.005 BCS-CRM 183/3 0.25 0.246 + 0.014 0.236 f 0.005 BNF-CRM 50.04 0.40 0.395 -I 0.012 0.399 k 0.005 BNF-CRM 50.01 0.52 0.55 + 0.02 0.51 f 0.02 * Mean and standard deviation of five analyses.conical flask. Add 5 ml of de-ionized water, 10 ml of concentrated hydrochloric acid and 2 ml of concentrated nitric acid, and warm gently. Cool the solution and dilute to 100 ml in a calibrated flask with de-ionized water. Transfer by pipette 10 ml of sample solution into a 50 ml conical flask. Add 0.5 g of sodium sulphite and warm gently until the sodium sulphite has completely dissolved. Cool the solution, add 2.5 ml of concentrated hydrochloric acid and dilute to 100 ml in a calibrated flask. Aliquots are analysed as described under Hydride Generation Procedure. The amount of Sb present is evaluated from a calibration graph (04.8 pg ml-1 of Sb) References Welz, B., Chem. Br., 1986.22, 130. Watling, R. J . , Anal. Chim. A m . 1977, 94, 181. Brown, A. A.. and Taylor, A.. Analyst, 1983, 108, 1159. Burns, D. T.. Atkinson, G . D., Chimpalee. N.. and Harriott, M., Fresenius 2. Anal. Chem.. 1988, 331, 814. Harriott, M., PhD Thesis. University of Belfast, 1984. Welz. B., and Melcher, M., Spectrochim. Acta, Part B , 1981,36, 439. Inui, T., Terada, S . , Tamura. H., and Tchinose, N., Fresenius Z. Anal. Chem., 1984. 318. 502. Godden. R. G.. and Thomerson. D. R . . Anafysr. 1980, 105. 1137. Determination of Total Tin in Acid Digests of Seaweed and Sediments Using Hydride Generation and Quartz-tube Electrothermal Atomization Michael Harriott, D. Thorburn Burns and Colin Donaghy Department of Analytical Chemistry, The Queen's University of Belfast, Belfast BT9 5AG The graphite furnace electrothermal atomization of total tin in acid digests of seaweed and sediments is prone to various interferences. 172 These interferences can be avoided by using hydride generation and quartz-tube electrothermal atomiza- tion processes.3" A variety of seaweed and sediment samples were analysed by using this procedure to establish a biological time scale indicator for organotin pollution in the marine environment .'-lo Preparation of Samples Sediments At low tide a core sampler was used to remove (50 x 10 cm) samples from specific locations around the sea lough at Strangford, Northern Ireland (Fig.1). Samples were placed onto (24 x 6 cm) lengths of PVC guttering and placed into labelled plastic bags for transit to the laboratory.On arrival, the plastic was removed and samples were frozen to -20 "C for 24 h (Fig. 2). Each sample was characterized by the method of - River Fig. 1 Location of Strangford Lough and site area Troels-Smith et al. 1 1 for the degree of darkness, stratification, elasticity, etc. After characterization, four 10 cm sections were removed from each sample by use of a mechanical saw. EachANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 Fig. 2 Sediment core samples 195 section was dried to constant mass at 80°C for 24 h and a Instrumentation particle size assessment made. Different particle size samples (0.5 g j of each section were digested with 2 ml of mixed acid (1 + 1 HN03-HCl) at 80 "C for 1 h in a laboratory-built Teflon digestion bomb (Fig. 3). Digested samples were cooled, up to 100 ml with distilled water.Graphite Furnace Electrothermal Atomic Absorption Spec- trometry A Perkin-Elmer Model 403 atomic absorption spectrometer hollow cathode lamp (286.3 nm; 8 mA). Signals were recorded by using a Philips PM 8251 chart recorder set at the 10 mV filtered through a 12 cm Whatman No. 7 filter-paper and made was equipped with a HGA-76 graphite furnace and a tin Fig. 3 Teflon digestion bomb Seaweed The common brown seaweed Ascophylfum nodosum (Fig. 4) was removed at low tide, along the water's edge, from the chosen site locations. The seaweed was placed into plastic bags for transit to the laboratory; on arrival the seaweed was removed from the bags, washed with distilled water, air dried (for 24 h j and segments dated from their position relative to the growing tips (Fig.5). Each segment was ground and sieved (120 pm) in order to obtain a homogeneous sample. Segment samples (1 g) were pre-ashed at 380°C until grey-white; ash samples were then transferred quantitatively into Teflon digestion bombs and digested with 2 ml of mixed acid (1 + 1 HN03-HCI) at 80°C for 1 h. Table 1 Furnace programme conditions Dry Ash Atomize Clcan TcmperaturcPC 150 800 2500 200 Tim& 30 30 2.5 5 Gas-stop Off Off On Off Fig. 4 Ascopliyllum nodosum Year 1988 1987 1986 1985 1984 L-1g83 Fig. 5 Post-dating of Ascophyllum196 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 range. Sample solutions were introduced into the graphite furnace with an Eppendorf microlitre pipette (50 pI) under the optimized conditions given in Table 1.The reproducibility of the analysis was improved by the use of a vanadium impreg- nated graphite tube.' The standard calibration graph for tin was linear up to 0.5 ppm with an RSD of 2% and a detection limit of 1 pg 1-1 of tin, respectively. However, atomic absorption signals for digested seaweed and sediment samples were distorted as illustrated (Fig. 6). Signal enhancement was not observed by the addition of known amounts of tin to digest samples. 0.1 ppm n Seaweed digests Fig. 6 mm min-1 Graphite furnace atomization profiles; chart speed, 300 Hydride Generation and Quartz T-Tube Electrothermal Atom- ization The Perkin-Elmer HGA-76 graphite furnace was removed from the Model 403 and replaced with a laboratory-built quartz T-tube electrothermal atomization unit, Fig.7. The spec- trometer conditions were as before and the hydride generator is as illustrated in Fig. 8. Table 2 Optimum conditions for the generation and detection of tin h ydride NaBH.., 2% m/v (2 ml) HCl 2% v/v (2 ml) N2 Temperature 980 "C 2000 cm3 min - 1 The optimized standard conditions for the generation and detection of tin hydride are summarized in Table 2. The standard calibration graph for tin hydride was linear up to 0.3 ppm, with an RSD of 3% and a detection limit of 0.5 pg I-' of tin, respectively. Atomic absorption signals for digested seaweed and sediment samples were normal, as illustrated in Fig. 9. Signal enhancement was also observed by the addition of known amounts of tin to both digests. Results and Discussion Sediments There were variations in the classification and particle size of each core sample and this ranged from large mineral particles (Grana suburruliu) at the surface (10 cm) to fine clay particles (Argillu steutodes) at the bottom (50 cm).The differences and similarities of each core were dependent on the physical and dynamic conditions of the sea-water within the site areas. The concentration, composition (fine sand) and particle size (200 mesh, 75 pm) were major contributing factors to the high Fig. 7 Quartz T-tube furnace concentration (400 pg g-1) of tin found in site No. 1. Although the composition of the core samples from the other site areas was different, tin (2 pg g-1) was only found in core samples containing sand particles of 200 mesh (75 pm) and a clay limestone appearance.Tin increased exponentially and linearly with particle size and depth in site No. 1 (Fig. 10). Therefore, the accumulation of tin in sedimentary material was a function of time, particle size and core depth. Seaweed The tin dating results for Ascophyllum nodosium (Fig. 11) indicate a high absorption of tin, by this plant, in site No. 1 during 1985-87 and also in site No. 2 between 1985 and 1988. Fig. 8 Hydride generatorANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 197 0.1 ppm Sn Seaweed digest I L! Fig. 9 Atomization profiles for tin hydride Results from all site areas indicate that both seaweed and sediments were more useful as monitors and time indicators of tin pollutants than was sea-water. 400 - 200 Depth 3 - 60 85 100 120 200 Mesh No.Fig. 10 Log tin content of sediment core from site No. 1 The results reflect environmental conditions at each site and permit a certain degree of historical tracing of water quality conditions in each site. 20 r l 0, o, 5. c v, . 10 0 1988 1987 1986 1985 1984 1983 1982 1981 Year Fig. 11 Tin distribution in Ascophyllum nodosum. 1 , Newtownards; 2, Strangford; 3 , Ardmillan: 4, Killyleagh; 5 , Kircubbin; and 6, Quoile Y.C. 1 2 3 4 5 6 7 8 9 10 11 References Donaghy. C., Harriott, M., and Burns. D. T., Anal. Proc., 1989, 26. 260. Burns, D. T., Dadgar, D., and Harriott. M., Analyst, 1984,109, 1099. Burns, D. T., Glockling, F.. and Harriott. M., Analyst, 1981, 106, 921. Burns, D. T., Harriott. M.. and Glockling, F., Fresenius 2. Anal. Chem.. 1987. 327, 7019. Harriott, M., PhD Thesis. The Queen’s University of Belfast, 1984. Harriott, M., Burns, D. T., and Glockling, F., The Biological Alkylation of Heuvy Elements, Royal Society of Chemistry. London. No. 66, 1988, p. 243. Woolstan. M. E . , Breek. W. G., and Vanloon, G. W.. Water Rev., 1982. 16, 687. Cairns, J.. and van der Schaline, W. H., Wafer Rev., 1980, 14, 1179. Eide, I., Myklestad, S., and Metsom, S., Environ. Pollut. Ser. A , 1980. 23. 19. Haug, A., Melsom. S., and Omang, S., Environ. Pollut., 1974, 7, 179. Troels-Smith, J., Karaterising. A., and Jordarter, L., Dan- murkes Geologiske Undersogelde, Scries 3, 1955, vol. 1, No. 10, pp. 1-173.

ISSN:0144-557X    

DOI:10.1039/AP9912800193

出版商:RSC    

年代:1991

数据来源: RSC

摘要:

ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 197 Ternary Complex Formation Between Alizarin Fluorine Blue, Lanthanoid Ions and Ethylenediaminetetraacetic Acid Type Chelating Ligands Brian Bingham, Rose Boyle, Marie M . Ferris and M. A. Leonard School of Chemistry, The Queen‘s University of Belfast, Belfast BT9 5AG Alizarin Fluorine Blue ( AFB) is 1,2-dihydroxyanthraquinon-3- ylmeth ylamine-N. N-diacetic acid. metal ions and EDTA-type chelating agents will produce such a reaction. A 2 : l ratio of AFB to EDTA is suggested as a selective reagent for the light lanthanoids. The ternary complex (AFB-La)?F has been used for many years as a means of determining low fluoride concentrations spectrophotometrically.1.’ At pH 4.5, AFB is yellow (A,,,, = 423 nm), (AFB-La)? is red (A,,;,, = 500 nm) and (AFB.La)?F is purple = 567 nm).Bingham3 observed that the 2 : 2 AFB:La complex formed a similar type of ternary complex with ethylenediamine- tetraacetic acid (EDTA) of A,,, 545 nm. Wc have investigated the composition of this complex and examined which other Experimental Absorption spectra were obtained with a Perkin-Elmer Lambda Nine ultraviolet-visible-near infrared recording spectrophotometer using 1 cm glass cells. The pH measure- ments were made using a Corning pH/ion meter (Type 135). Reagent Solutions All solutions were prepared with doubly distilled water. Alizarin Fluorine Blue, 1.00 X 10-3 mol dm-3. Weigh 0.385 g of carefully dried AFB (BDH or Aldrich) into a small beaker. By successive treatment with small portions of a solution of 0.4 g of sodium hydroxide in 20 cm3 of water, dissolve the AFB198 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 0.60 H G I 0.48 8 0.36 m e s 2 0.24 0.12 0 E D C B I 400 500 600 700 Wavelengthlnm Fig.1 Spectra illustrating ternary complex formation. cLa = 1 X 10-4 rnol dm-3. cAFB + cEDTA = 1 x 10-4 mol dm-3. Also shown is the spectrum of AFB alone at cAFB = 5 X 10-5 rnol dm-3. pH = 4.6, 1 cm cell. Molar ratio of AFB:EDTA-A, 0: 10; B, 1:9; C, 2:8; D, 3:7; E, 4:6; F, 5 : 5 ; G, 6:4; H, 7:3, I, 8:2: J, 9: 1; and K, 1O:O mOl dm-3, CAFB = 0-1 x lop4 m01 dm-3, CEDTA = 1 x 10-4-o and transfer the solution into a 1 1 beaker. Add 0.2 g of hydrated sodium acetate, dilute to about 800 cm3, then reduce the pH to about 5 by using dilute HC1 and a pH meter. Transfer the solution into a 1 1 calibrated flask and dilute to the mark with water.Filter into a brown glass bottle. Lanthanum nitrate, 1.0 x 10-2 mol dm-3. Dissolve 4,3303 g of lanthanum nitrate hexahydrate in water and dilute to 1 1. Standardize by direct titration with standard 1 x 10-2 rnol dm-3 EDTA at pH 6 using Xylenol Orange as indicator. Dilute this solution to 1.00 X 10-3 or 5.00 X 10-4 mol dm-3 as required. EDTA solution, 1.0 X 10-2 rnol dm-3. Dissolve 3.7244 g of disodium EDTA dihydrate in water and dilute to 1 1. Standardize by direct titration at pH 6 with standard 1 X 10-2 rnol dm-3 lead nitrate using Xylenol Orange as indicator. Dilute to 1.00 X 10-3 or 5.00 X 10-4 rnol dm-3 as required. EDTA-lanthanum complex, 1.00 X 10-3 rnol dm-3. Mix appropriate volumes (about 10 cm3) of 1 X 10-2 rnol dm-3 EDTA and 1 x 10-2 rnol dm-3 lanthanum solutions in a 100 cm3 beaker and dilute to about 70 cm3.Adjust the pH to 4.6 by using the pH meter and dilute to 100 cm3. 0.6 2 8 0.4 C m e s a n 0.2 0 400 500 600 700 Wavelengthlnm Fig. 2 Rate of ternary complex formation. cLa = 1 x 10-4 mol dm-3, CAFB = 5 X mol dm-3, cEDTA = 5 x 10-5 rnol dm-3. pH = 4.6, 1 cm cell, T = 20 "C. These constituent ratios are not in accordance with the composition of the complex; nevertheless, the effect is well illustrated. Spectra taken at 5 min intervals: 1,3 min after mixing; and 2, after 1 h. 3, EDTA absent, cLSl = 5 x 10-5 mol dm-', cAPB = 5 x 10-5 mol dm-3 Acetate buffer solution, p H 4.6, 2 rnol dm-3. Dilute 120 cm3 of glacial acetic acid to about 800 cm3.Adjust the pH to 4.6 by using concentrated sodium hydroxide solution and dilute to 1 1. Results Relevant Spectra A 20.0 cm3 volume of 5.00 x 10-4 rnol dm-3 lanthanum nitrate and 2.0 cm3 of pH 4.6 acetate buffer were transferred by pipette into each of a series of 100 cm3 beakers and diluted to about 60 cm3 with water. Then 0, 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 cm3 of 5.00 x 10-4 rnol dm-3 AFB and 20, 18, 16, 14, 12, 10, 8, 6, 4, 2 and 0 cm3 of 5.00 x 10-4 rnol dm-3 EDTA were added to successive beakers. The solutions were mixed, diluted to 100 cm3 and allowed to stand for 1 h. The spectra were recorded against 0.04 rnol dm-3 acetate buffer. These spectra are shown in Fig. 1. Rate of Ternary Complex Formation This is fairly slow. A 10.0 cm3 volume of 5.00 x 10-4 rnol dm-3 EDTA and 10.0 cm3 of 5.00 X 10-4 mol dm-3 AFB were mixed and diluted to about 60 cm3.A 2.0 cm3 volume of pH 4.6 acetate buffer and 20.0 cm3 of 5.00 x 10-4 rnol dm-3 lanthanum nitrate were added. The mixture was mixed rapidly and diluted to 100 cm3. Spectra were recorded against a 0.04 rnol dm-3 acetate buffer blank at 5 min intervals over a period of 1 h. The result is shown in Fig. 2. For all subsequent studies a standing time of 1 h was used. 0.50 5 In % 0.375 w m ar 0.25 5 5: n a 0.125 0 25 50 75 100 La (%) 100 75 50 25 0 EDTA (Yo) Fig. 3 Job plot for variation of lanthanum and EDTA concentrations. CAFB = 5 X low5 rnol dm - 3 . cEDTA = 0-1 x 10-4 mol dm-3, cLiI = 1 x 10-4-0 mol dm-'. I cm ccll, pH = 4.6. h = 545 nm Composition of the Complex This was investigated initially by using Job's method of continuous variation, holding the concentration of one con- stituent constant and varying the concentration of the other two while retaining a constant sum.Variation of lanthanum and ED T A concentrations Into a series of 100 cm3 calibrated flasks were placed 5.00 cm3 of 1 .00 x 10-3 mol dm-3 AFB, 3.0 cm3 of pH 4.6 acetate buffer solution and 40 cm3 of water. Then n cm3 of 1.00 x 10-3 mol dm-3 EDTA and (10 - n ) cm3 of 1.00 x 10-3 rnol dm-3 lanthanum nitrate were added. The solutions were diluted to the mark, mixed well and allowed to stand for 1 h . The absorption spectrum of each solution was recorded against 0.06 rnol dm-3 acetate buffer and the absorbance at 545 nm noted. The result is shown in Fig. 3. A 3: 1 ratio of lanthanum to EDTA is evident.Variution of A FB and lanthanum concentrations The procedure was as described above; the volumes of reagents employed were 5.00 cm3 of 1.00 x 10-3 rnol dm-3 EDTA, n cm3 of 1.00 X 10-3 rnol dm-3 AFB and (25 - n) cm3 ofANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 199 r---- 2 0.50 13 7 0 25 50 75 100 La ( % I I 1 I I I 100 75 50 25 0 AFB (%) J o b plot for variation of AFB and lanthanum concentrations. rnol dm-?, CL', = 2.5 Fig. 4 cl x 10-4-41 mot dm-;. pW = 4.6. 1 cm ccll. h = 545 nm 1.O() X 10-? rnol dm--3 lanthanum nitrate, where n = 0, 5 , LO, 15, 20 or 25. The result is shown in Fig. 4. A 3:2 ratio of lanthanum to AFB is evident. A = 5 x 10-' rnol dm-'. CAFE = 0-2.5 x Vuriutiorz o f A FH und E D TA concentrations The procedure was as described above; the volumes of reagents wcre: 10.0 cm3 of 1.00 X 10-3 rnol dm-3 lanthanum nitrate, rz cm3 of 1 .OO X 10-3 mol dm--3 AFB and (10 - n ) cm3 of 1.00 X l0k3 rnol dm--i EIITA.The result is shown in Fig. 5 . The ratio of AFB to EDTA is 2 : I . 0.75 7 I E In 5 0.50 m a, S m +? a 0.25 1) 0 25 50 75 100 AFB (%) 100 75 50 25 0 EDTA (%) Fig. 5 Job plot for variation of AFB and EDTA concentrations. cLa = 1 x lop4 mol dm-3, cAFD = 0-1 x 10-4 rnol dm-3. CEDTA = 1 x lo-'- 0 rnol dm-3. pH = 4.6, 1 cm cell, h = 545 nm Vuriutron of the concentrations of the binary complexes (AFB-La)? and EDTA.La Into a series of 100 cm3 calibrated flasks wcre placed 0, 2 , 4 , 5 , 6, 8 and 10 cm-3 of 1.00 X LO-' rnol dm-3 EDTAeLa solution, n cm3 o f 1 .OO X 10- rnol dm-? AFB and n cm3 of 1.00 x 10-3 mol dm-3 lanthanum nitrate solution, where n = 20, 16, 12, L O , 8, 4 and 0.A 3.0 cm3 volume of pH 4.6 acetate buffer was added to each flask and the solution made up to volume. The procedure was continued as described above. The result is shown in Fig. 6 . This is a particularly clear indication of ternary complex formation as, if this did not occur, a straight line between the extremities would result. The combining ratio of (AFB-La)? to EDTA-La is 1 : 1. From the cvidence of these four Job plots the composition of the ternary complex is (AFB)?La3(EI1TA). Determination of the Composition of the Complex by Simplex Optimization4 A triangular diagram three-point (triangular) simplex optimi- zation approach w;is tried to determine the ratio of AFB.lanthanum and EDTA which would give maximum absorbance I I I - 0 25 50 75 100 EDTA.La (%) (AFB.LaI2 (%) L I I 1 100 75 50 25 0 Fig. 6 Job plot for variation of (AFB.La)2 and EDTAeLa concentra- tions. ctDT*.La = 0-1 x loL4 mol dm-3, c(AFR.La), = 1 X 10-j-0 mol dm-3. pH = 4.6, 1 cm cell, h = 545 nrn at 545 nm with a constant total concentration of 1 X mol dm-3. First exp e rim en ta I point Into a 100 cm3 calibrated flask were placed 1.8 cm-? of 1 x mol dm-3 AFB, 3 em3 of acetate buffer, 40 cm3 of water and 5.6 cm3 of I x 10-3 rnol dm-3 EDTA. The solution was mixed thoroughly and 2.6 cm3 of 1 X 10-3 rnol dm--? lanthanum nitrate were added. The basic procedure was then followed. The other two points of the first triangle used ( a ) 3.0 cm3 of 1 x 10-3 rnol dm-3 AFB, 2.6 cm3 of 1 x 10-3 rnol dm-3 lanthanum and 4.4 cm3 of I x 10-3 rnol dm-3 EDTA; (b) 1.8 cm3 of 1 x 10-3 rnol dm-3 AFB, 3.8 cm3 of L x 10-3 mol dm-3 lanthanum and 4.4 cm3 of 1 x 10-3 rnol dm-3 EDTA.The simplex procedure was continued, generating equilateral triangles by reflecting away from the lowest absorbance reading of each set of three vertices. Step size was reduced as the summit was approached. The result is shown in Fig. 7 and yields a complex composition of 36% AFB, 47% lanthanum and 17% EDTA o n a molar basis, which is very close to the (AFB)?La3(EDTA) found previously. This stoichiometry appears reasonable on the basis of the number of ligand atoms involved and the probable number of coordination sites provided by the lanthanum ions. Ethylenediaminetetraacetic acid is a hexaden- tate ligand and AFB, from past experience ,5 has a maximum of six ligand atoms; hence between them the organic molecules provide 18 ligand atoms.This matches the 18 coordination sites provided by the three hexacoordinate lanthanum ions. Ability of Other Lanthanoids to Produce This Reaction Solutions (1.00 X 10-3 mol dm-3) of the cheaper lanthanoids were prepared from appropriate salts or by dissolving the oxide in dilute nitric acid. 100% EDTA 100% La3+ 100% AFB Fig. 7 Triangular diagram simplex approach to determining the composition of the ternary complex. For all points cAFB + cLa + CEDTA = 1 X lo-' mol dm--3. Absorbance measured at 545 nm, pH = 4.6, 1 cm cell200 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 Procedure Into each of two 100 cm3 beakers (A and B) were placed 12 cm3 of 1 x 10-3 mol dm-3 AFB and 12 cm3 of 1 x 10-3 rnol dm-3 lanthanoid solution.The solutions were adjusted to a volume of about 40 cm3 and a pH of 4.0. Into a third beaker (C) were placed 4 cm3 of 1 X 10-3 mol dm-3 EDTA and 4 cm3 of 1 x 10-3 rnol dm-3 lanthanoid solution. This was adjusted to about 25 cm3 and pH 4.0. The contents of beakers A and B were then transferred into two 100 cm3 calibrated flasks (A and B) and 3 cm3 of pH 4.6 acetate buffer solution added to each. The contents of beaker C were then added to flask B. Hence the binary complex solution was in flask A and the possible ternary complex solution in flask B. The absorption spectrum of each solution was then recorded against 0.06 mol dm-3 acetate buffer.The result is shown in Fig. 8 in which A,,, (LA-AFB- EDTA) - A,,, (LA-AFB) is plotted against lanthanoid (LA) atomic number. It can be seen that ternary complex formation diminishes rapidly as the lanthanoid series is progressed; this is analogous to the behaviour of the ternary fluoride complex as demonstrated by Greenhalgh and Riley.6 Beyond holmium not only do the binary and possibly ternary complex A,,, values coalesce, but also the spectra become identical. 57 58 59 60 61 62 63 64 65 66 67 68 La Ce Pr Nd Pm Sm Eu Gd Tb Dy Ho Er Element and atomic number Fig. 8 Variation of ternary complex formation with atomic number of the lanthanoid used. Concentration of the ternary complex if com- pletely formed, 6 X mol dm-3. pH = 4.6, 1 cm cell Ability of Other EDTA-type Chelators to Produce This Reaction A 1.00 X 10-3 rnol dm-3 solution of each of the following chelating agents was prepared in distilled water with the addition of sodium hydroxide if necessary: iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), diethylenetriaminepenta- acetic acid (DTPA), ethyleneglycolbis(aminoethyl)tetraacetic acid (EGTA) and trans- 1,2-diaminocyclohexane-N, N , N’ ,A”- tetraacetic acid (CDTA).The procedure used was as described in the previous section except that in this instance 1 x 10-3 rnol dm-3 lanthanum nitrate was used and the EDTA solution was replaced by each of the analogues in turn. For IDA and NTA, 8 cm3 of solution were used. Table 1 summarizes the ability of ‘EDTA-like’ chelators to produce a ternary complex in the presence of lanthanum and AFB.It is evident that only CDTA, whose structure is very similar to that of EDTA, formed the ternary complex to any appreciable extent. In fact, the absorption spectrum of the AFB-La-CDTA complex is almost identical with that of the corresponding EDTA complex. A zero A,,,, shift corresponds also to identical spectra but this section presupposes that ternary complex formation will lead to a spectral change. Influence of pH on Ternary Complex Formation A 5 x 10-5 mol dm-3 solution of the ternary complex was prepared by using 5 cm3 of 1 x 10-3 mol dm-3 EDTA, 10 cm3 of 1 X loa3 mol dm-3 AFB and 15 cm3 of 1 x 10-3 rnol dm-3 lanthanum. The pH of the solution was varied in 0.5 unit steps from 3.0 to 7.0 using formate, acetate and hexamine-HN03 buffers. The resultingspectra are shown in Fig.9. It can be seen Table 1 Ability of EDTA-like chelators to producc a ternary complex in the presence of lanthanum and AFB h,,,, (ternary complex) - Chelator h,;,, (binary complex)/nm EDTA 41 CDTA 42 EGTA 9 NTA 5 IDA 0 DTPA 0 that complex formation is virtually complete in a pH 4.5 acetate buffer. The fact that for all spectra A = 0 in the 750-800 nm region shows that the complex is in true solution. The spectral enhancement produced by using an acetate buffer is noteworthy. Electrical Charge on the Complex The nature of the charge on the (AFB)2La3(EDTA) complex was investigated by studying the effect of the addition of equimolar solutions of large cations and anions to the ternary complex solution.Solutions (1.0 X 10-3 rnol dm-3) of the following salts were prepared: sodium dodecyl sulphate, sodium tetraphenylborate, sodium anthraquinone-2-sulpho- nate, tetrabutylammonium iodidc, tetraphenylarsonium chloride, cetylpyridinium chloride (CPC) and cetyltrimethyl- ammonium bromide (CTAB). A 1.0 x 10-4 rnol dm-3 solution of (AFB)2La3(EDTA) was prepared by mixing 50 cm3 of 1 X 10-3 mol dm-3 AFB, 25 cm3 of 1 X 10-3 mol dm-3 EDTA, 3 cm of pH 4.6 acetate buffer and 75 cm3 of 1 x 10-3 rnol dm-3 lanthanum nitrate and diluting to 250 cm3. In each of a series of seven 100 cm3 beakers were mixed 20 cm3 of 1 x 10-4 mol dm-3 ternary complex and 2.0 cm3 of of 1 X 10-3 rnol dm-3 pairing agent. The mixtures were inspected after 24 h. Only the cations cetylpyridinium and cetyltrimethylammonium yielded a purple precipitate; this would suggest that the ternary complex is anionic in nature.A large amount of the cetylpyridinium salt was precipitated, filtered off, washed with water and dried. Found: C, 54.41; H, 6.36; N , 4.13. [(AFB)2La3(EDTA)].[CsHsNeC16H33]2 requires C, 52.00; H, 5.43; N, 4.05%. Analytical Applications Although the main purpose of this work was to investigate the nature of the ternary complex, a suggested application might 0.8 0.6 m +? 0, n 0.4 0.2 0 400 500 600 700 Wavelengthhm Fig. 9 Intluence of pH on formation of the tcrnary complex. cternary if formed completcly, 5 x 10-5 rnol dm-3. 1 cm cell. pH: A. 3.0 (formate); B, 3.5 (formate); C, 6.0 (hexamine-HN03); D , 6.5 (hexamine-HN03); E, 7.0 (hexamine-HN03): F, 4.0 (acetate); G, 4.5 (acetate); H, 5.0 (acetate); and I, 5.5 (acetate)ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 20 1 0.9 0.8 0.7 0.6 al C a 0.5 0 ' 0.4 0.3 0.2 0.1 0 2 4 6 8 10 12 14 16 18 Volume of 10-3 mot dm-3 metal solution addedkm3 Fig.10 Determination of lanthanum (cerium and praseodymium) by reaction with AFB and EDTA. CAFB = 1 + lopJ rnol dm-3, CEDTA = 5 x 10-5 mol dm-3. cLa = 0-1.5 x mol dm-3. pH = 4.6,l cm cell, h = 545 nm. The graph obtained by substituting lead for lanthanum is also shown be the absorptiometric determination of lanthanum(mj , cerium(ii1) and praseodymium(rr1). To a series of 100 cm3 calibrated flasks add 10 cm3 of 1 x 10-3 rnol dm-3 AFB, 5 cm3 of 1 x lo-' rnol dm-3 EDTA, 2 cm3 of pH 4.6 acetate buffer and dilute to about 70 cm3.Add, with swirling, 0-15 cm3 of 1 X 10-3 rnol dm-3 lanthanum nitrate, dilute to the mark, wait I h then measure the absorbance at 545 nm against a blank containing all the constitutents except lanthanum. The unimpressive calibration graph is shown in Fig. 10. However, the selectivity is reasonable; a correspond- ing graph for lead is shown on the same diagram and similar graphs are given by iron(iii), zinc(ii), cobalt(i1) and copper(i1). Erbium(iI1 j and gadolinium(l1l) cause greater interference; hence 14 cm3 of 1 X 10-3 rnol dm-3 Er3+ gives A = 0.49 and 14 cm3 of 1 x 10-3 rnol dm-3 Gd3+ gives A = 0.70. Again, a mixture of 10 cm3 of 1 x 10-3 rnol dm-3 AFB, 2 cm3 of acetate buffer and 10 or 15 cm3 of 1 X 10-3 rnol dm-3 lanthanum nitrate would be very selective towards EDTA-type chelators in a qualitative or quantitative capacity. Discussion Although the possible analytical applications of this reaction do not, at first sight, seem to be of importance, this work is being reported because of the striking parallels with the valuable AFB-lanthanum-fluoride reaction. Hence the stoi- chiometry of the complexes is similar, viz., (AFBj2La2F and (AFB)zLa3(EDTA), as are the spectra. The rate of formation and sensitivity to lanthanoid atomic number are also virtually the same. In the field of luminescence spectroscopy such complexes might provide a means of energizing the central metal ion to yield an emission of almost atomic line sharpness as, for example, is observed with the salicylate-Tb-EDTA complex .7 References Belcher. R., Leonard, M. A . , and West, T. S., J. Cliem. Soc., 1959. 3577. Johnson, C. A . , and Leonard, M. A., J. Pharm. Pharmacol., 1961. 8 (Suppl.), 164T. Bingham, B . . MSc Project, The Queen's University of Belfast, Belfast. 1986. Long. D. E., Anal. Chim. Acfa, 1969, 56, 193. Langmyhr, F. J . , Klausen, K. S., and Nouri-Nekoui, M. H., Anal. Chim. Acra, 1971, 57, 341. Grecnhalgh, R . , and Riley, J. P.. Anal. Chim. Acfa, 1961, 25. 179. Dagnall, R. M.. Smith. R., and West. T. S . . Analyst. 1967, 92. 358.

ISSN:0144-557X    

DOI:10.1039/AP9912800197

出版商:RSC    

年代:1991

数据来源: RSC

摘要:

202 ANALYTICAL PROCEEDINGS. JUNE 1991, VOL 28 Mass Spectrometer The Sciex (R) Model API I11 is a triple quadrupole mass spectrometer linked to a liquid chromatograph for separation. Ions are created at atmospheric pressure, rather than inside a vacuum system, with little or no heating; this atmospheric pressure ionization technique is applic- able to polar, thermally labile molecules. The technique .is particularly appropriate to the analysis of pharmaceutical prod- ucts, surfactants and fine chemicals. The instrument is not limited to LC-MS or LC-MS-MS techniques, as liquid or dis- solved samples can be introduced by a simple infusion pump, by flow injection analysis or by capillary zone electrophore- sis. Perkin-Elmer Ltd., Maxwell Road, Beaconsfield, Buckinghamshire HP9 IQA.Atomic Absorption Software Designed to operate on a wide variety of PCs, a software package to enhance the data handling capacity of the makers’ PU9200X and PU940OX atomic absorp- tion spectrometers has been based on Microsoft’s EXCEL spreadsheet, running in the Windows graphic environment. It allows easy manipulation of analytical data, transferred direct from the spec- trometer to the PC, and permits the user to select numerous options to produce high-quality final reports. The data can be saved in several formats for use with other third party software, such as databases and LIMS systems. Philips Analytical, York Street, Cambridge CB1 2PX. Flow Injection Analysis Preconcentration Kit The FIAS-200 flow injection system for atomic spectrometry combines the advan- tages of the mercury/hydride techniques with those of the flow injection technique.The concentration of many trace elements in different matrices is too low to be directly determined with flame AAS and lengthy sample preparation is required to preconcentrate and then extract these elements. The new preconcentration kit for FIA-flame AAS provides automatic on-line element preconcentration for flame AAS using the FIAS-200 flow injection system. Perkin-Elmer Ltd., Maxwell Road, Beaconsfield, Buckinghamshire HP9 1QA. Spectroscopy Software The new QUANT+ software package for multi-component quantitative analysis is ideally suited to infrared, ultraviolet and fluorescence spectroscopic techniques. Applications can range from the determi- nation of a single property to the determi- nation of 15 separate physical or chemical properties, using as many as 150 calibra- tion spectra.Traditional spectroscopic methods for quantitative analysis need either isolated peaks for each property or a knowledge of all the interfering species in the sample. QUANT+ overcomes these limitations by using an advanced chemometric approach. Perkin-Elmer Ltd., Maxwell Road, Beaconsfield, Buckinghamshire HP9 IQA. Grating for ICP Spectrometry The 3410 ICP instrument offers a guaran- teed resolution of 0.013 nm over the range 165-800 nm. However, for some analyses, notably of rare earth elements, even higher resolution is sometimes necessary. The 3410 ICP is, therefore, offered with an alternative grating which has a greater line density and, hence, better resolution. The 3600 line mm-* grating produces a guaranteed resolution of 0.008 nm over the wavelength range 165-533 nm.Higher resolution will, of course, not eliminate all spectral interferences but the PlasmaVi- sion 10 software can correct for spectral overlap and background emission. ARL Applied Research Laboratories SA, En Vallaire, 1024 Ecublens, Switzer- land. Spectroradiometer System A new spectroradiometer system per- forms ultraviolet irradiance measure- ments by ensuring effective stray light rejection and it features PC compatibility. The IL1700/760D/791 double monochro- mator spectroradiometer is a digitally controlled system featuring scanning speeds of 10, 20, 50, 100, 200, 500 and 1000 nm min-1 with digital wavelength and digital signal readouts.Literature is avail able. International Light Inc., 17 Graf Road, Newburyport, MA 01950, USA. Spectroscopy Products Perstorp Analytical Ltd. have combined the latest addition to their range of spectroscopy products, Guided Wave, with the existing instruments from NIRSystems and Tecator within a single group concerned with marketing, applica- tions and customer training. Perstorp Analytical Ltd., Cooper Road, Thornbury, Bristol BS12 2UW. Liquid Chromatography Columns for Protein Purification Porozorb cartridges efficiently remove Triton X-100, sodium dodecyl sulphate and other detergents from protein solu- tions without loss of protein. ‘These ready to use chromatography columns, which contain Amberlite XAD-4 or XAD-16 polymeric hydrophobic resins, can also be used to isolate, purify or concentrate pharmaceutical and biological com- pounds from aqueous streams. Porozorb cartridges come in 250, 500, 1000 and 1500 ml sizes, each cartridge coming with a certificate of analysis, assuring that it is sterile and pyrogcn-free. Supelchem, Shire Hill, Saffron Walden, Essex CB 11 3AZ.Chromatograph The Carlo Erba Vega Series 2 gas chro- matograph is ideal for routine QC appli- cations. Up to eight methods can be stored for the Vega GC and A200S robotic autosampler. It is also an excellent low-cost option for research applications, featuring a high-performance column oven, cold on-column injection and series mounting of detectors. Fisons Instruments, Sussex Manor Park, Gatwick Road, Crawley, Sussex RHlO 2QQ. Dye-Ligand Affinity Adsorbents A new range of purpose-designed Mimetic dye-ligand affinity adsorbents offer greatly improved chemical stabilities to reduce ligand leakage to exceptionally low levels.They provide robust replace- ments for traditional affinity media based on textile dyes which are susceptible to dye leakage, particularly at alkaline pH. The new adsorbents offer longer column life, high capacities, reproducible separa- tions and can be treated with caustic alkalis for cleaning and depyrogenation of packed columns. They are manufactured to GMP standards. Affinity Chromatography Ltd., Free- port, Rallasalla, Isle of Man. De-cappers The DCB-20 de-capper for 20 mm caps is available in two sizes: 11 and 20 mm. It is ideal for the environmentally and safety conscious wishing to separate all four elements: the sample, the glass.the cap and the seal. Chromacol Ltd., Glen Ross House, Summers Row, London N12 OLD. Flow Injection Analyser The FIA-FLO is an automatic singlc- or dual-valve system which provides total flexibility to the user; it can be changed and set up to monitor different chemis- tries. I t is ideal for use in monitoring sea and river pollution, including tests forANALYTICAL PROCEEDINGS, JUNE 1991. VOL 28 203 Burkhard scientific FIA- FLO flow injection analyser aluminium, and in chemical or process plant monitoring, food processing and manufacture or process plant monitoring. It includes a CFI-X or CF2-X and CFI-UV ultraviolet detector. The sample charger is available with a 40 place capacity or serpentine with up to 300 sample cups.An x-y sampler option is available. Burkhard Scientific (Sales) Ltd., P.O. Box 55 Trading Estate, Eskdale Road, Uxbridge, Middlesex UB8 2RT. Supercritical Fluid Multiple Extractor The SFE-703 is a self-contained unit taking advantage of the solvating power of supercritical fluids to reduce or elimi- nate the use of solvents in the sample preparation laboratory. It features mul- tiple cell capability, extraction pressures up to 680 bar, flow measurement and a unique plug free resistant collection tech- nique. The oven, which can be heated up to 150 "C, accommodates up to eight cells with as much as 32 ml capacity. Control of the collection temperature and the unique design of the collection vials ensure uni- form recovery of light and heavy analytes.The SFE-703 is expected to replace liquid- based extraction devices for most sample preparation activities. A brochure is ava i 1 able . Dioncx (UK) Ltd., 4 Albany Court, Camberley, Surrey GU15 2PL. Multiple Gas Analyser The Model MGA 1600 on-line multiple gas analyser monitors up to 16 com- ponents from as many as 50 sample streams, with a typical analysis time of 12 s per stream. In addition to detecting specific masses, it can scan each sample stream for unspecified components which might contaminate the process. System calibration, generally required at only YO d intervals, can be performed auto- matically and verified immediately. The Model MGA 1600 is fully programmable and controlled by an industry-standard PC. Perkin-Elmer Ltd., Maxwell Road, Beaconsfield, Buckinghamshire HP9 IQA.Water Analyser The Tecator Aquatec automated water analyser is capable of testing most sources of water for ammonia, chloride, nitrate, nitrite and phosphate on a batch or individual sample basis. The self-con- tained method cassettes hold everything required for each type of analysis, and everything from sample input to result printout is automatically controlled, while pre-weighed, optimized reagents mini- mize error. Perstorp Analytical Ltd., Cooper Road, Thornbury, Bristol BS12 2UW. Weighing Machines Included in the Emeraude range of com- mercial and industrial weighing machines is the Emeraude 20, which has an accu- racy five times better than that of other models currently on the market. The range consists of high precision scales and weighing machines, with 6000 grades from 6 to 3000 kg.Models 3 and 19 have been approved to Class 111 by the French Metrology Department and are approved for commercial use. The Model 20 has all the features of the Model 19, with the addition of extra high resolution: touch- ing the High Resolution key increases the accuracy five times, giving a resolution of 1 in 30 000. When connected to a printer the Model 20 makes a useful management tool, providing date, time, totals, etc. Precia Industries Ltd., 15A Bourne Enterprise Centre, Borough Green, Sevenoaks, Kent TN15 8DG. Platform Mixers Two new models, Vari-Mix and Speci- Mix, offer a choice of mixing speeds, from 1 to 20 rev min-1, and variable mixing pitch, from 1 to 48 ". A special reversible non-slip rubber pad holds test-tubes securely, and the user-friendly design allows for ease of loading and unloading, even without turning the unit off. Radleys, Shire Hill, Saffron Walden, Essex CB11 3AZ.GoggleBoxes The GoggleBox range now includes four models: the original GoggleBox for spec- tacles, GoggleBox I1 for safety goggles, GoggleBox 111 'The Mini GoggleBox for safety spectacles', and the new Goggle- Box IV for storing smoke escape hoods. The last has been designed to dispense rapidly and safely smoke escape hoods and is ideal for use in isolated or haz- ardous laboratories and industrial sites. Radleys, Shire Hill, Saffron Walden, Essex CBll 3AZ. Imaging Photon-detector System An imaging photon-detector system with digital signal processing electronics achieves count rates of up to 300000 photons s-1.A number of application- specific software packages are available, and a full complement of standard image processing capabilities provide the user with facilities for image enhancement, pseudo-colour presentation, image arith- metic and logical operations, intensity profiling and three-dimensional plots. Instrument Technology Ltd., 29 Castle- ham Road, St. Leonards-on-Sea, East Sussex TN38 9NS. PC-PC Network LIMS EasyLIMS, an innovative PC-PC network LIMS, is now available for use with Microsoft Windows 3, providing a straightforward way to integrate Easy- LIMS data with other third party soft- ware, such as Microsoft's Excel spread- sheet, using standard file transfer and cut and paste techniques. Beckman, Progress Road, Sands Indus- trial Estatc, High Wycombe, Bucking- hamshire.LIMS Module Lab Manager, Beckman's digital VAX- based LIMS system, can now be enhanced204 ANALYTICAL PROCEEDINGS, JUNE 1991, VOL 28 with an automatic reporting tool, thus promoting the ‘paperless laboratory’. The new module, ETR (event triggered reporting), allows users to configure auto- matic reporting activities based on LIMS sample and test events, using simple ‘fill-in-the-blanks’ screens. For example, ETR affords the benefit of automatically generating labels when samples are logged into the LIMS, with different label formats for each sample classification. Worksheets can be produced automatic- ally prior to testing and warning reports can be issued whenever tests fail or results are rejected.Heckman, Progress Road, Sands Indus- trial Estate, High Wycombe, Bucking- hamshire. Mathematical Package Macintosh-based RESOLUTION elimi- nates the tedium of routine calculations and checking, provides powerful tools for one-off calculations and simplifies the interpretation of raw data or complicated functions through its interactive graphical presentation facilities. Among many other mathematical operations, RESOL- UTION can handle Fourier analysis, complex numbers, units conversion, geometry functions, statistics and dif- ferential equations. ECS Ltd., Cooper House, Dam Street, Lichfield, Staffordshire WS13 6AA. LIMS Barcode Package ACCOMPLIS, which is intended for medium and large research and quality control laboratories, uses barcodes not only for sample labelling, but also to identify analysts and storage locations, and to issue a wide range of commands.JCl Chemicals and Polymers Ltd., P. 0. Box No. 1, Billingham, Cleveland TS23 1LB. Molecular Graphics Software The TBM PC version of NEMESIS, a high-performance molecular graphics program, is announced. The Apple Mac- intosh version was launched in August, 1990. A uniform price of f500 will apply to both versions. Oxford Molecular Ltd., Terrapin House, South Parks Road, Oxford OX1 3UB. Literature A catalogue, Reference Materials for Spectrometric Analysis, contains a com- prehensive listing of various samples (Fe-, Al-, Cu-, Zn-, Ti- and Zr-base) and high-purity metals. It is a clear and comprehensive guide for users requiring samples for optical emission and XRF spectrometry.Spectro A. I . GmbH., Boschstrasse 10, D-4190 Kleve. Spectro Live, Number 13, October 1990, features articles on a new sequential ICP spectrometer with dual fixed grating monochromators, the new Spectro X-Lab which combines the advantages of energy dispersive XRF analysis with detection limits comparable to wavelength disper- sive XRF, and others. Spectro A. 1. GmbH., Boschstrasse 10, D-4190 Kleve. An application note on the principles and applications of infrared microscopy is available. Typical applications include the identification of inhomogeneities in poly- mer films, analysis of single fibres and investigation of the different layers of laminates. Perkin-Elmer Ltd., Maxwell Road, Beaconsfield, Buckinghamshire HP9 1QA. A detailed technical specification and leaflet describe the EG5000 small spot electron source, a general purpose medium spot size source for Auger analy- sis and sample imaging, under the control of the 0-5 keV EG5000 control unit.The EG5000 can produce a fine focus spot of 5 pm and comes complete with video signal processing electronics, built-in CRT monitor and integrated TV rate scan unit. VSW Scientific Instruments Ltd., Warwick Road South, Old Trafford, Manchester M16 OJT. Chromatography Newsletter deals with VarioPrep HPLC columns, which have adjustable end fittings allowing compen- sation of the dead volume at the column inlet without opening the column itself. Also discussed are Nucleogel GPC col- umns for the separation of water-soluble compounds, and FS-Lipodex columns, which can be used for the separation of enantiomers. Field Analytical, Investment House, Queens Road, Weybridge, Surrey KT13 9UT. An applications brief discusses the useful- ness of micellar electrokinetic capillary chromatography for the separation of opiates using the P/ACE 2000 capillary electrophoresis system. Beckman, Progress Road, Sands Indus- trial Estate, High Wycombe, Bucking- hamshire. A product literature pack entitled ‘Humidity Solutions . . .’ shows a range of humidity measurement instrumentation. It covers a comprehensive range of port- able and on-line hygrometers and gives full details of the CERMET hygrometer, which uses the Michell CerTSense ceramic sensor for on-line measurement of dewpoint/moisture content in indus- trial and process gases. Michell Instruments Ltd., Unit 9, Nuf- field Close, Nuffield Road, Cambridge CB4 1SS. A Water Analysis booklet gives details of several analyses, including pH, alkalinity, calcium and magnesium in one sample, chemical oxygen demand, dissolved oxy- gen, and trace amounts of lead, cadmium and copper. Radiometer Ltd., The Manor, Manor Royal, Crawley, West Sussex RHl0 2PY.

ISSN:0144-557X    

DOI:10.1039/AP9912800202

出版商:RSC    

年代:1991

数据来源: RSC