摘要:

Proceedinas - - - - - - ~~of the Analytical Division ofThe Chemical Society117118118127130139142143143144CONTENTSReports of MeetingsSummaries of Papers'Determination and Interpretation ofRare-earth Abundances in Rocksand Minerals''Elwell Award Meeting''Replacement of Biological Methodsby Chemical and PhysicalMethods'Equipment NewsCorrespondenceConferences and MeetingsPublications ReceivedObituary-J. 6. Attrill146 Analytical Division DiaryVolume 13 No 5 Pages 117-146 May 197PADSDZ 13(5)117-I 46( 1976)ISSN 0306-1 396May 1976PROCEEDINGSOF THEANALYTICAL DIVISION OF THE CHEMICAL SOCIETYOfficers of the Analytical Divisionof the Chemical SocietyPresidentD. W. WilsonHon. SecretaryP. G . W. CobbSecretaryMiss P.E. HutchinsonHon. Treasurer Hon. Assistant SecretariesJ. K. Foreman D. I. Coomber, O.B.E.; D. C. M. Squirrel1Editor, ProceedingsP. C. WestonProceedings is published by The Chemical Society.Editorial: The Director of Publications, The Chemical Society, Burlington House, London, W1 V OBN.Telephone 01 -734 9864. Telex 268001.Subscriptions (non-members) : The Chemical Society, Publications Sales Office, Blackhorse Road, Letch-worth, Herts., SG6 1 HN.Non-members can only be supplied with Proceedings as part of a combined subscription with The Analystand Analytical Abstracts.@ The Chemical Society 1976VOLUME 4,1974Annual Reports on AnalyticalAtomic SpectroscopyThis comprehensive and critical report of developments in analytica I atomicspectroscopy has been compiled from over 1550 reports received fromworld-wide correspondents who are internationally recognised authorities inthe field and who constitute the Editorial Board. In addition to surveyingdevelopments throughout the world published in national or internationaljournals, a particular aim has been to include less widely accessible reportsfrom local, national and international symposia and conferences concernedwith atomic spectroscopy.Paperbound 280pp 8$”x 6” 0 85990 245 4 f 12.00(Still available Vols. 1-3 covering 1 971 to 1973)Obtainable from : The Publications Sales Officer, The ChemicalSociety, Blackhorse Road, Letchworth, Herts., SG6 1 H

ISSN:0306-1396    

DOI:10.1039/AD97613FX017

出版商:RSC    

年代:1976

数据来源: RSC

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MAYThursday, 20th, 10.45 a.m. : BetchworthBiological Methods G Y O U ~ Suvnmey Meeting :Visit to Beecham Research J,aboratories,Brockham Park, Betchworth, Surrey.Tuesday and Wednesday, 25th and 26th:GlasgowScottish Region on “Atomic AbsorptionTuesdaji, 25211, 2 p.m.-“Principles o€ Atomic Absorption Spectro-metry,” by TV. B. Rowston.“Spectral, Physical ancl Chemical Inter-ferences and Their Control in RoutineAnalysis,” by J. M. Ottaway.Demonstyation Session on the setting up andoptimisation of atomic-absorption instru-ments.Spectrometry.”Wednesday, 2W1, 9 a.m.-“Clinical Analysis,” by G. S. Fell.“Agricultural Analysis,” by A. M. Ure.“Food and Water Analysis,” by I. Dale.“Preconcentration Techniques,” by A. M.TJre.Demonstration Session on analytical appli-cations of flame atomisers.“Recent Developments in Instrument De-sign,” by K.J . Mills.“Filament and Furnace Atomiscrs,” by J . M.Ot taway .Demonstration Session on llelves’ cup, mer-cury cold vapour, hydride generation cellsand filament ancl furnace atoniisers.Room C133 of the Thomas Graham Building,University of Strathclyde, Glasgow.Wednesday, 26th, 2.15 p.m. : LoughboroughC‘Jivomatogvaphy and Electvoplzovesis GyouPand Midlands Region on “AnalyticalChemistry of Drug Metabolites.”“i.2nalytical Problems Involved in the Meta-bolism of Drugs ancl Foreign Compounds,”by J . W. Gorrod.“The Use of Thin-layer Chromatography inthe Quantitative ,\nalysis of Body Fluids,”by D. A. Stopher.“Gas - Liquid Chromatographic Methods forthe Analysis of Drug Metabolites,” by-4.C. Moffat.“The Application of HPLC to Drug Meta-bolism,” by G. Skellern.Lecture Theatre U020, Brockington Ex-tension, University of Technology, Lough-borough, Leicestershire.Analytical Division DiaryPrinted by Heffers Printers Ltd Cambridge EnglandJUNETuesday, Sth, 3.15 p.m.: LondonAqzalytical Division.“Contributions to the Analytical Chemistryof Rhenium,” by Professor N. Jordanov.Laboratory of the Government Chemist(Conference Room, Annex A407), CornwallHouse, Stamford Street, London, S.E. 1.Thursday, loth, 6.30 p.m.: Birminghamilfidlazzds Region.“Contributions to the L4nalytical Chemistry ofLecture Theatre 101, Haworth Building, TheRhenium,” by Professor X.Jordanov.University, Edgbaston, Birmingham.Tuesday, 15th, 2 p.m.: LondonOriginal Papers Meeting.Joint Plzawaacezttical Analysis GVOILP :For full list of papers see p. 143.Pharmaceutical Society of Great Britain, 17Hloomsbury Square, London, 1V.C. 1.Friday, 18th, 12 noon: GlasgowScottish Region.“A General Purpose Atomic Spectrometer forthe Analysis of Solutions and Solids byAbsorption, Fluorescence or EmissionSpectroscopy,” by A. IValsh, FRS.Chemistry Department, University of Strath-clycle, Glasgow.Thursday, 24th, 10.30 a.m. : BristolA tomic Spectvoscopy Gvoup and Westel/%Region : Current Awareness Symposium on“Xon-flame Atomic Absorption by Electro-thermal Atomisation.”“History, Development and Advantages ofElectrothermal Atomisation,” by IT7, J .Price.“Interferences and Optical Design,” by K. C.Thompson.“Ultra Clean Sample Handling Techniques,”by J . F. Woolley.“Clinical Applications of ElectrothermalAtomisation for AAS,” by H. T. Delves.“Difficulties in the Analysis of Water,” byL. Ranson.“Electrothermal Atomisation a t the Labora-tory of the Government Chemist,” byJ. Warren.Discussion on “Do You Believe the Result ? ’ Iintroduced by C. A. Watson.School of Chemistry, The University, Bristol

ISSN:0306-1396    

DOI:10.1039/AD97613BX019

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

Vol. 13 No. 5 May 1976 of the Analytical Division of the Chemical Society Reports of Meetings CS Annual Congress The Analytical Division participated in the CS Annual Congress, held at the University of Glasgow from April 5th to 9th, 1976. The central theme of the Congress was “Chemistry and Energy,” and the AD organised two Symposia : “Developments in Analytical Atomic Spectroscopy” on April 6th and 7th; and “Analysis in the Energy Industries” on April 8th.On April Gth, the following papers were pre- sented and discussed : Plewavy L e c t w e : “State of Dcvelopinent of Atomic Absorption and Atomic Fluorescence Spectrometry with Furnaces,” by H. Massmann ; “Carbon Furnace Atomic Emis- sion Spectrometry,” by F. Shaw, J . M. Ottaway and D. Littlejohn; “Some Recent Studies with Electrothermal Atomisers used in AAS,” by M.J . Adams and G. F. Kirkbright; Invited Lectuve : “Practical Developments in Atomic Fluorescence Spectrometry,” by T. S. West ; “Determination of Zinc and Cadmium in Bio- logical Samples by Atomic Fluorescence Spec- trometry,” by G. s. Fell, D. C. Hough, F. E. R. Hussein and J. M. Ottaway; “A Kinetic Theory of Atomisation for AAS using a Graphite Furnace Atomiser.Applications to Interfer- ence Studies and Matrix Control,” by C. W. Fuller; “Peak Area Measurement of Transient Signals in Atomic Absorption Spectrometry,” by J . E. Cantle; “The Analysis of High Solid Content Liquid Samples for Trace Metals Using Temperature Controlled Carbon Rod Atomisa- tion,” by M. D. Mayhew. On April 7th, the first paper was the fifth Theophilus Redwood Lecture by Professor R.Belcher, entitled “The Elements of Organic Analysis,” and a scroll was presented to Pro- fessor Belcher by the AD President, Mr. D. w. Wilson. The programme then continued with the following papers : “Interferometric Atomic Line Profile Measurements in Hollow Cathode and Electrodeless Discharge Lamp Sources, ” by Pvesepztatzon OJ scvoii oy tne H u pveszaent, iv1 Y.u . w . Wzlson, to the f i f t h Theoplbalus Redwood Lecturer, Pvofessov R. Belchev (L). G. F. Kirkbright, D. G. Beva6 and S. L. Castleden ; “The Determination of Trace Ele- ments in Metals by Atomic Absorption Spec- trometry with an Induction Furnace. Direct Analysis of Solid Samples,” by J . B. Headridge; Iwvited L e c t w e : “Why Plasma Torches ? ” by S.Greenfield ; “Some Recent Analytical Applica- tions of MECA Spectroscopy,” by S. L. Bogdan- ski; “The Application of an Atmospheric Pressure Ion Source to the Measurement of Isotope Ratios a t Trace Levels in Solution by Mass Spectrometry,” by li. J. Anderson and A. L. Gray; “The Application of Flame and Carbon Furnace Atomic Absorption Spectro- metry to Routine Rock Analysis, with Special Reference to the Determination of Trace amounts of Strontium and Gallium,” by J.Warren ; “Some Recent Developments in the Analytical Applications of Candoluminescence, ” by A. Townshend. On April Sth, the following papers were presented : “Analytical Developments in the Nuclear Industry,” by V. M. Sinclair; “Analysis in the Electrical Supply Industry,” by G.I. Goodfellow; “Progress in Analysis in the Solid Fuel Industry,” by H. C. Wilkinson; “Analysis in the Petroleum Industry,” by A. Quayle; “An Integrated Approach to the Analysis of Air- Pollutant Polynuclear Aromatic Hydro- 117118 Proc. Analyt. Div. Chew. Soc. carbons,” by K. D. Bartle; “Application of the Britain, 17 Bloonisbury Square, London, W.C.2. High Performance ‘SOLFA’ On-Line Analyser The Chair was taken by the Chairman of the to Measure Total Sulphur in Petroleum Distil- Group, Mr. G.F. Phillips. The following lates and Residual Fuels,” by C. F. Gamage; office bearers were elected for the forthcoming “Identification of Crude Oils by Luminescence year : Chaivman-Mr. S. C. Jolly. Honovnvy Techniques,’’ by P. John and I. Soutar. Secvetavy-Mr. J. C. Deavin, William Warner & Co. Ltd., Eastleigh, Hants. Members of Com- mittee-Mr. E. Addison, Dr. F. J. Bryant (representing the AD), Dr. J. M. Calderwood, Mr. J. E. Fairbrother, Ur. L). C. Garratt The Annual General Meeting of the Group was (representing the Pharmaceutical Society), held a t 6.30 p.m. on Thursday, January P5th, Mr. C. A. Johnson, Mr. D. H. Mitchell, Mr. G. F. 1976, a t the Pharmaceutical Society of Great Phillips and Dr. A. F. Turner. RARE-EARTH ABUNDANCES IN ROCKS AND MINERALS Joint Pharmaceutical Analysis Group

ISSN:0306-1396    

DOI:10.1039/AD9761300117

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

118 RARE-EARTH ABUNDANCES IN ROCKS AND MINERALS Proc. Analyt. Div. Chew. Soc. Determination and Interpretation of Rare-earth Abundances in Rocks and Minerals The following are summaries of four of the papers presented at a Joint Meeting of the Scottish Region with the Mineralogical Society and the Edinburgh and Glasgow Geological Societies held on December 19th, 1975. The geological papers on interpretative aspects may be sub- mitted for publication in AIinevalogical Magazine.Rare-earth Elements in Chondrites as Normalising Factors in Geochemistry P. J. Potts Depavtment of’ Eavth Sciences, T h e Open Univevsity, Wulton Hull, Milton Keynes, MK7 6A A The rare-earth elements (KEE) comprise the sequence of 14 elements following lanthanum in the periodic table. Although their chemical properties are very similar, the REE are distinguished by a progressive reduction in the size of each element from lanthanum through to lutetium, this being from 0.106 1 nm (ionic radius of La3+) to 0.084 8 nm (ionic radius of Lu3+).This “lanthanide contraction” proceeds contrary to the expected trend in the Periodic Table and is a result of an increasing positive charge on the nucleus of each REE more strongly contracting the negatively charged electron cloud, the size of which would otherwise remain approximately constant.The REE are present in parts per million amounts in all igneous rocks, and the analysis of these elements has become increasingly important in geochemistry in recent years. As the REE span a discrete range of ionic radii, each element will partition itself in slightly different proportions between the available ionic lattice sites in the various mineral phases that make up a rock.Therefore, by measuring the way in which the REE abundances are fractionated in a particular rock, geochemists can obtain information about such processes as partial melting and fractional crystallisation, which can take place during the formation of a rock.A problem with this approach is that when the abundances of REE in a rock are plotted on a logarithmic scale against increasing atomic number [Fig. 1 ( a ) ] , a saw-toothed pattern results. This is a manifestation of the Odd0 - Harkins observation that elements of even atomic number occur in greater abundance than neighbouring elements of odd atomic number.This effect is itself due to the extra stability of nuclei that contain even numbers of protons and neutrons compared with those composed of even - odd combinations of neutrons and protons. Clearly, it is very difficult to interpret any trends or fractionation patterns from the abun-May, 1976 RARE-EARTH ABUNDANCES I N ROCKS AND MINERALS 119 dance data in Fig.l ( a ) . chondrite REE abundances as a reference point. Geochemists have therefore turned their attention to considering I I I I I I I I I I I I I I I , La C e Pr Nd(Pm)SmEu Gd Tb Dy Ho Er Tm Yb L u I , I I I I I I I I I I I I I l l l l l l l l l l l l l l l Fig. 1. (a) Rare-earth element abundances in USGS standard Basalt BCR-1 in parts per million (from a compilation by Flanaganl) .(b) Rare-earth element abundances in chondrite (p.p.m.) (from reference 2 with additional values for Pr, Tb, Ho and Tm of 0.123, 0.052, 0.078 and 0.034, respectively). (c) Chondrite-normalised abundances of BCR-1 (p.p.m./chondrite), Chondrites are a type of meteorite composed of iron magnesium silicate and containing small rounded “chondrules” of olivine and pyroxene.When the numbers of different types of meteorites seen to fall to Earth are compared (irons, 4.6y0, stony irons, 1.5% ; anchondrites, 7.8%; chondrites, 86.1y0),3 it is clear that by far the largest proportion are chondritic meteo- rites. In fact, it has been estimated4 that 1 000-10 000 tons of this material fall to Earth daily. This has led to the proposal that chondrites represent the primitive material from which the Earth was originally composed.Thus, all terrestrial rocks could be derived from chondrites by geochemical fractionation processes. In any event, the REE composition of chondrites [Fig. l ( b ) ] represents a convenient re- ference for comparison of terrestrial REE abundances. I t has become conventional to normalise REE values relative to chondrite by dividing each KEE abundance by the120 RARE-EARTH ABUNDANCES IN ROCKS AND MINERALS Proc.Analyt. Div. Chem. SOC. corresponding chondrite abundance. The resulting data are plotted on a logarithmic scale against atomic number. Such “chondrite-normalised plots” [Fig. 1 (c)] usually show a smooth variation of REE composition from element to element. The first is that the REE abun- dances in chondrites themselves vary.The most widely used chondrite values are those of Frey et ~ 1 . ~ (composite chondrite), Masuda et aZ.2 (Leedey chondrite) and Nakamura6 (average of 10 ordinary chondrites); perhaps the most complete review is that of Nakamura. The second problem involves promethium. Chondrite-normalised data are never presented for promethium because, of the 13 known isotopes, each is radioactive with a half-life of less than 30 years.’ Any promethium originally in the Earth’s crust would have rapidly decayed over geological time.The natural abundance of promethium is not quite zero, however, as it is formed in minute amounts during the spontaneous fission of naturally occurring uranium. The analysis of rock samples for the REE using chondrite-normalised plots has made some important contributions in such fields as terrestrial geochemistry,s ocean floor basalt^,^ par- tition coefficient datalo and lunar geology.ll However, because of the problems of low abun- dances and the complications of the silicate matrix, some very sophisticated techniques must be employed in the analysis of rocks for the REE.Two problems with this approach must be mentioned. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. References Flanagan, F. J., Geochim. Cosmochim. Acta, 1973, 37, 1189. Masuda, A., Nakamura, N., and Tanaka, T., Geochim. Cosmochim. Acta, 1973, 37, 239. Mason, B., “Meteorites,” John Wiley & Sons, New York, 1962. Mason, B., “Principles of Geochemistry,” Third Edition, John Wiley & Sons, New York, 1966.Frey, F. A., Haskin, M. A., Poetz, J. A., and Haskin, L. A., J . Geophys. Res., 1968, 73, 6085. Nakamura, N., Geochim. Cosmochim. Acta, 1974, 38, 757. Moeller, T., “The Chemistry of the Lanthanides,” Chapman and Hall, London, 1963. Haskin, L. A., Helmke, P. A., raster, T. P., and Allen, R. O., in Brunfelt, A. O., and Steinnes, E., Editors, “Activation Analysis in Geochemistry and Cosmochemistry,” Universitetsforlaget, Oslo, 1971, p.201. Frey, F. A., Bryan, W. B., and Thompson, G., J . Geophys. Res., 1974, 79, 5507. Jensen, B. B., Geochim. Cosmochim. Acta, 1973, 37, 2227. Brunfelt, A. 0. and Steinnes, E., Talanta, 1971, 18, 1197. Determination of Rare Earths by Neutron-activation Analysis J. E. Whitley Scottish Universities Research and Reactor Centre, East Kilbvide, Glasgow, G75 OQ U In neutron-activation analysis, the amount of an element in a sample is determined by measuring the radioactivity of an isotope of that element produced when the sample is irradiated, and comparing it with the radioactivity produced in a known amount of the same element irradiated and counted under the same conditions.The technique has been used most frequently in recent geochemical rare-earth analyses because of its high sensitivity (between and 10-l1 g for rare earths) and because recent developments in instrumentation have facilitated non-destructive analyses by relatively inexperienced personnel.Limitations of the method are that it does not differentiate between different chemical forms of an element and that the comparison of activities is only valid for elements of constant isotopic com- position.Samples are usually between 0.1 and 1.0 g, this being the amount that produces acceptable count rates for the elements to be determined, while the dose rate from the sample is not excessive after a typical irradiation of 6 h in a flux of 10l2 neutrons cm-2 s-l. Standard solutions are usually prepared from spectrographically pure rare-earth oxides and calibrated by titration with EDTA.Because of the high neutron absorption of some rare earths, sample activation can be depressed when the content of certain rare earths exceeds 20 pg.l The presence of this effect can be detected by comparing the specific activities in duplicate samples of differing masses.When the effect is significant, account can be taken of it by measurement of flux depressionMay, 1976 RARE-EAKTH ABUNDANCES I N ROCKS AND MINERALS 121 with an internal standard, by diluting the sample with an element of low neutron absorption cross-section, or by the method of standard addition. Such measures have been found necessary only for the analysis of rare-earth concentrates and separated minerals with high rare-eart h contents.The major detectable activity a few hours after activation of geological material is usually found to be 15.0-h sodium-24, and this generally precludes the measurement of rare earths with comparable half-lives unless a chemical separation is carried out. While the development of high-resolution y-ray spectrometers [germanium (lithium) detectors with high-capacity multi-channel analysers] has made it possible to determine most rare earths instrumentally, a radiochemical separation of all of the rare earths facilitates the determination of all of the naturally occurring rare earths with better sensitivity and accuracy.Recent trends have been to separate the rare earths as a group for germanium (lithium) counting in order to overcome some of the limitations of the purely instrumental approach.The radiochemical method is essential for samples of low rare-earth content, and has been used for the analysis of chondritic material.2 Up to 14 rare earths have been determined in terrestrial samples by this method, with an accuracy between &2 and k5y0. The require- ments for the separation of rare earths by ion exchange is the main reason for the limited use of this method.Most recent analyses have been carried out instrumentally by variations of the procedure described by Gordon et aL3 Samples are counted at several decay times up to 2 months after activation, but a dozen samples can be irradiated together and processed as a batch. Parti- cular care must be exercised in interpreting the resulting y-ray spectra, in order to eliminate erroneous results due to interfering photopeaks from other elements.While some rare earths can be determined with errors of less than -+5% by this method, most of the heavy rare earths are more difficult to determine, and for these the counting errors can be as high as &30y0. The number of elements that can be determined is also dependent on the magnitude of inter- ferences, but between eight and eleven rare earths have regularly been determined by this technique.By radiochemically separating the rare earths as a group, the major interferences can be eliminated, although some rare earths still interfere with each other in the resulting y-ray spectra. While the chemistry is less demanding than a full separation by ion exchange, carriers must be added for all of the rare earths, and their chemical yields measured or inter- polated as fractionation can occur during the chemical processing.The determination of up to 14 rare earths by this approach has been described but the determination of 11 with an accuracy between &2 and &loyo is a more realistic assessment of what can be a~hieved.~ The extent of interfering nuclear reactions has not always been considered in descriptions of the methods which have been discussed.While in most instances these reactions can be shown to be insignificant, a detailed consideration of them by Allen et ~ 1 . ~ showed that an adjustment of results for cerium and neodymium may be required for samples in which the uranium content is more than 10% of that of the rare earth ~oncerned.~ I t is apparent from the geochemical literature that there is an increasing interest in the distribution of rare earths in rocks and minerals.With some aspects of the fine structure of abundance patterns unresolved (systematic analytical errors or real effects ?), further work is needed with improved accuracy for the maximum number of elements.It is expected that most activity in the near future will involve neutron-activation analysis followed by group separation, particularly to achieve an improvement in accuracy for the heavy rare earths. While a better accuracy can be achieved by mass-spectrometric isotope dilution, this technique is limited to the determination of ten rare earths, and the facilities required for this approach are not so widely available.References 1 . 2. 3. 4. 6. Turkstra, J., and Van Droogenbrock, M. A., J Z S. A f v . Chem. Inst., 1975, 28, 61. Schmitt, K. A., Smith, R. IT, Lasch, J . E., Mosen, A. W., Olehy, D. A., andvasilevskis, J., Geochim. Gordon, G. E., Randle, I<., Goles, G. G., Corliss, J. B., Beeson, M.H., and Oxley, S. S., Geochim. Potts, M. J., Early, T. O., and Herrman, A. G., 2. Analyt. Chem., 1973, 263, 97. Allen, R. O., Haskin, L. A., Anderson, M. R., and Miiller, O., J . Aadioanalyt. Chem., 1970, 6, 115. Cosmochim. Acta, 1963, 27, 577. Cosmochim. Acta, 1968, 32, 369.122 Determination of Rare-earth Elements by Mass-spectrometric Isotope Dilution RARE-EARTH ABUNDANCES IN ROCKS AND MINERALS Proc.Analyt. Din. Chem. Soc. R. J. Pankhurst Department of Geology and Mineralogy, Univevsity of Oxfovd, Oxfovd, OX1 3BD Mass-spectrometric isotope dilution has long been recognised as a very accurate and sensitive method for the determination of trace elements in a wide variety of matrices. A calibrated amount of artificially enriched isotope (tracer, or spike) is added to the sample and the iso- topic composition of the mixture is measured.Knowing the isotopic composition of the normal element, the amount present can be determined from the relationship where X and Y are the masses of normal and spike elements, respectively, and A , and A , are their respective relative atomic masses, N , and S , are the atomic abundances of the kth isotope in the normal and spiked elements, respectively, and N,,, Sik, Mi, are the ratios of the ith and Kth isotopes in the normal element, spike element and measured mixture, respectively.Hence the main requirement of the method is that any element determined should have more than one naturally occurring isotope, one of which (preferably a minor one) is available in an artificially enriched state (occasionally, long-lived radioactive isotopes can be utilised) .loo 1 CeO + * Yb + i: i Fig. 1. Mass spectra of the rare-earth elements observed using single Ta filament ionisation. The heights of the columns represent the relative abundance of isotopes for each of the natural elements. Isotopes preferentially enriched in the spike elements are indicated by an asterisk.True atomic mass is indicated on the scale at the bottom: interference could occur wherever different elements have isotopes in the same vertical line. Shading shows partial chemical separation into three groups by the ion-exchange method, except for Ba, which can occur in all (but is mostly ionised as Ba+). The only major corrections required are for interference of 142hTd on 142Cc and (15*Sm + 138Ce) on 138La.For the rare-earth elements, this requirement restricts the application of the method to lanthanum, cerium, neodymium, samarium, europium, gadolinium, dysprosium, erbium, ytterbium and lutetium. Fortunately, this covers the complete range adequately, and gives maximum control on the anomalous abundance of europium. Suitable enriched isotopes ofMay, 1976 RARE-EARTH ABUNDANCES I N ROCKS AND MINERALS 123 all of these elements are available from the Oak Ridge National Laboratory, Tennessee, although the maximum enrichment for lanthanum-138 is only 7.86%.For the analysis of rock and mineral samples, the spikes are added prior to decomposition with hydrofluoric acid - nitric acid in a PTFE pressure vessel.This procedure ensures complete isotopic equilibration. Subsequently, the rare earths are chemically separated from the sample on a Dowex 1 ion-exchange column by using glacial acetic acid - nitric acid eluting solutions.1 For convenience in mass spectrometry, the rare earths are then split into three fractions (Lu-Dy ; Gd-Nd; Ce and La) on a second column by using methanol - nitric acid mixtures.It should be noted that other chemical separation schemes using Dowex 50 - hydrochloric acid ion exchange are also comm0n.~93 The mixed organic solvent - nitric acid method achieves better separation from barium. After separation, the fractions are analysed on a suitable solid-source mass spectrometer (9- or 12-in radius). Using single tantalum filament ionisation, some elements are observed as the metal ion and some as a compound metal oxide ion, as shown in Fig.1. Because of the large number of rare-earth isotopes, and the chemically similar nature of barium, there is a considerable possibility of isobaric interference. This interference, however, is virtually eliminated by (a) the chemical separation described above, (b) the different ionisation tem- peratures of different elements and (c) careful selection of isotope pairs for ratio measure- ment.4 In practice, small corrections have to be applied to cerium and lanthanum, although only in the latter instance are they critical, because of the very low abundance of lanthanum-138. TABLE I CONCENTRATIONS OF REE IN USGS STANDARD ROCKS All data from Hooker et aZ.4 Concentration, p .p.m. r Rock La Ce Nd Sm Eu Gd DY Er Yb BCR-1* 24.2 53.5 29.3 6.67 1.94 6.76 6.33 3.67 3.48 hGV-1 38.1 68.7 32.1 5.83 1.54 4.76 3.55 1.82 1.68 GSP-1" 182 425 203 26.1 2.22 11.1 5.49 2.13 1.47 G-2 97.7 160 54.8 7.27 1.34 3.97 2.11 0.83 0.60 F'CC- 1 - 0.07 0.051 0.0006 0.029 0.014 0.010 0.012 0.03 * Mean of duplicate analyses. An independent check can be made by measuring more than one isotope pair for most elements.Further indications of accuracy are derived from results on standard rocks supplied by the US Geological Survey, and the smooth variations of abundance with atomic number (except for europium) after normalising to the abundance in some common cosmic material, usually chondrite meteorites. From such considerations, it is clear that the accuracy of the determination is generally better than 2%, except for lanthanum and lutetium.Blanks arc extremely low (less than 3 W9 g) and abundances down to 0.01 p.p.m. are easily determined. Results obtained on some standard rocks are given in Table I. The method described here was developed jointly with P. J. Hooker and R. K. O'Nions. Research grants were provided by the Natural Environment Research Council and the Royal Society.References 1. 2. 3. 4. Korkisch, J., and Arrhenius, G., Analyt. Chew., 1964, 36, 850. Schnetzler, C. C., Thomas, €I. H., and Philpotts, J . A., AnaZyt. Chew., 1967, 39, 1888. Shimizu, N., Yb. Cavnegie Instvz Wash., 1974, 73, 941. Hoolrer, P. J., O'Nions, K. K., and Pankhurst, R. J., Chem. Geol., 1975, 16, 189.124 Determination of Rare Earths in Rocks and Soils by Spark-source Mass Spectrometry RARE-EARTH ABUNDANCES IN ROCKS AND MINERALS Proc.Analyt. Div. Clzem. SOC. A. M. Ure and J. R. Bacon Macaulay Institute f o v Soil Reseavch, Cvaigiebucklev, Abevdeen, A B 9 2Q J The application of spark-source mass spectrometry to the determination of rare-earth abun- dances in rocks and soils forms part of a wider development programme designed to produce a method for determining the contents of almost all of the minor and trace elements in these materials.Spark-source mass spectrometry is a simultaneous multi-element technique with wide element coverage and relatively uniform and high sensitivity over the whole mass range from lithium to uranium. To retain this survey capability and avoid sample contamination, it is necessary to keep sample pre-treatment to a minimum.For these reasons, a method of standardisation, based on synthetic powder standards and on data for analysed standard rock samples, has been developed to achieve satisfactory analytical accuracy. An AEI MS702R spark-source mass spectrometer (SSMS) with photographic plate record- ing is used.To allow non-conducting powder samples to be sparked, electrodes are made from mixtures of finely ground (<lo0 pm) sample and a pure (99.999%) aluminium con- ducting powder. The latter has certain advantages over the more commonly used graphite conductor. Carbon is not monoisotopic and has a lower atomic mass and, as a result, graphite produces a more complicated mass spectrum with lines due to polyatomic carbon ions a t regular intervals throughout the mass range.Interfering, coincident carbon species occur at three of the rare-earth lines and in particular that at m/e 169 makes the determination of monoisotopic thulium virtually impossible. Monoisotopic aluminium, on the other hand, interferes only at the gadolinium line at m/e 162 and several other alternative gadolinium isotopic lines are available.A 50-mg chisel-shaped sample electrode is hydraulically pressed in a PTFE mould from a 1 + 1 mixture of finely ground sample and an aluminium powder containing 125 p.p.m. of indium in oxide form as an internal standard. This sample is sparked against a dagger- shaped pure aluminium foil counter electrode. About 12 exposures are made for each sample on the photographic plate with total ionic charge levels ranging from 0.1 to 600 nC, and a continuous recording of the optical transmission of each exposure on the developed plate is made with a scanning microphotometer.As barium occurs in rocks and soils in convenient amounts, a plate calibration graph can be prepared using the seven barium isotopes whose known isotopic abundances, and hence relative intensities, range from 0.1 to 71%.The plate calibration graph of Seidel density, - 100 O/, transmission 1 , veysus relative intensity is linear for the Ilford Q2 plates em- ) ploye-d"over a 50-fold relative intensity range. unknown and internal standard lines are obtained. calculated from the relative intensities using the equation From this graph, relative intensities for the The concentration of the element is where CA and Cr are the concentrations of the isotope.(A) of the element being determined and the known concentration of indium in p.p.m.a. (p.p.m.atomic), respectively, N A and N I are the measured relative intensities of the unknown isotope (A) and indium, and FA/FI is a constant calculated, on a theoretical basis, for each clement relative to indium, to take account of the three main factors which determine the sensitivity.These three factors are (1) the variation of plate sensitivity with isotopic mass, (2) ionisation potential and (3) involatility. A further conversion from p.p.m.a. to p.p.m.w. (p.p.m. on a weight basis) provides semi- quantitative values for the elemental concentrations.The trace element contents, obtained in this semi-quantitative way, for the US Geo- logical Survey Standard Rock BCR-1 (basalt) are generally high compared with accepted literature values and within the rare-earth group certain element contents stand out as being&fay, 1976 RAKE-EARTH ABUNDAKCES I N ROCKS AND MINERALS 125 much too high, as a probable consequence of superpositional interference on the mass spectral lines measured.At these relatively high mass numbers, the most probable interfering species are oxides of barium or other rare earths and these make the analysis of europium, gadolinium, dysprosium and terbium difficult. A relative sensitivity coefficient (RSC), defined here as SSMS value/literature value and based on the values obtained for BCR-1, could be introduced and used to correct the semi-quantitative SSMS values.As this would depend on the unlikely assumption of constancy for the ratio of the interfered to the inter- fering species in all sample types, this approach would increase the accuracy only for samples whose composition is almost identical with that of BCR-1. The alternative method outlined below corrects the interference effects before calculating and applying RSCs.TABLE I COMPOSITION OF UNIGNITED SYNTHETIC SOIL BASE SiO, 62 K2S04 3.5 Fc203 5 MgO Component Content, "/o Component Content, yo 20 CaCO, 3 2 1 Na,CO, 3.5 TiO, A set of synthetic rare-earth standards was prepared from pure rare-earth oxides in a synthetic soil base in order to (1) show that oxide interferences do occur, (2) apply a correction scheme to minimise interference effects and (3) obtain RSC values based on these corrected line intensities, which could justifiably be applied to samples of widely different types.The standards were prepared in a synthetic soil base, shown in Table I, approximating in major composition to a soil derived from an intermediate igneous rock or an average shale. Three different standards, (Nos.1, 2, 3, Table 11), and appropriate dilutions of them, were prepared in order to segregate the interfering and interfered species as far as practicable, with a fourth standard containing all the rare earths and barium at levels typical of a rock or a soil (No. 4, Table 11). TABLE I1 STANDARDS IN IGNITED (1 050 "C) SOIL BASE No.Standard 1 2 3 1% Nd; and dilutions 4 1 "/o rare earths (all rare earths except Gd, Sm and Nd) ; and dilutions 1% Gd, Sin and 10% Ba; and dilutions Complete standard; 1000 p.p.m. Ba + 100 p.p.m. Gd, Nd, Sm + 10 p.p.m. other rare earths (see text) The spectrum of soil base with only neodymium added, for example, shows that the isotope intensity pattern for the neodymium species is repeated for the neodymium oxide species with almost the same magnitude.However, measurements of line intensities over several exposures show that the ratio "NdlGO/"Nd is not a constant from one exposure to another and consequently it is not possible to devise a correction based on a relationship between metal and metal oxide. On the other hand, it was found that the ratio of two oxides always equals the ratio of the two parent metal ions, e.g.and therefore a correction for a 143Nd160 interference can be obtained by a measurement of the magnitude of the 144Nd160 species. The neodymium oxide lines coincide with some gadolinium and dysprosium lines, but also, and more important, with the monoisotopic terbium-159 line. Hence the terbium-159 line must be corrected for neodymium oxide interference before the terbium concentration can be calculated.The spectrum of soil base plus barium, samarium and gadolinium shows a similar pattern126 PYOC. Awalyt. Div. Chewz. SOC. of oxide interferences. However, the intensities of samarium oxide lines are low and, even on the highest exposures normally made for soils and rocks, are probably insignificant.This is not true of barium oxides, which give moderately strong lines at m/e 151 and 153, the two europium isotopes. In order to obtain accurate results for europium, it is therefore necessary to apply a correction for the barium oxide interferences. Such a correction is straightforward and easy to apply. The two lines a t m/e 151 and 153 each consist of a europium isotope plus an oxide of a barium isotope and so can be represented by the two equations RARE-EARTH ABUNDANCES IN ROCKS AND MINERALS Measured R I (m/e 151) = RI (151Eu) + R I (135Ba160) Measured RI ( m / e 153) = RI (153E~) + RI (137Ba160) where R I is relative intensity.equations can be written in the form of two simultaneous equations: Using the isotopic abundances of the two europium and two barium isotopes these two R I (m/e 151) = R I (151Eu) + R I (135Ba160) x RI ( 1 3 5 ~ ~ 1 6 0 ) 11.41 52*21 x RI (151Eu) + - 6.58 R I (m/e 153) = __ 47.79 and solved t o give R I (151Eu) = 2.70 RI (wz/e 151) - 1.56 RI (m/e 153) This correction uses only the measured intensities of the lines m/e 151 and 153 and there is no extrapolation of results from other exposures or other samples to the spectrum being inter- preted.Similar equations can be written for all of the lines representing rare-earth isotopes, and in all instances except one, unique solutions for the actual rare-earth intensities without inter- ferences can be obtained. A correction for the possible interference of 159Tb160 on the 175Lu line is not feasible because lutetium-176 is usually too weak to be measured and terbium is monoisotopic.However, the concentration of terbium itself is usually low and hence the contribution of terbium oxide is likely to be too small to affect the determination of lutetium. Using this correction scheme, all of the lines in the rare-earth region can be resolved into the different ionic species making up the measured peak and hence the intensities due to each rare-earth isotope alone can be calculated.This scheme was applied to the synthetic standard sample (No. 4, Table 11) containing all of the rare earths together with barium and, knowing its actual composition, RSCs were calculated for all of the rare earths. The correction scheme and these RSCs were then applied to measured line intensities obtained for BCR-1, with the results shown in Table 111.Compared with the original uncorrected semi-quantitative values, the corrected figures are much closer to, but in general somewhat higher than, the literature values quoted and show the improvement that this correction and standardisation scheme makes. It is em- phasised that the corrected figures have been obtained independently of the BCR-1 literature values.However, such a scheme is of use only if it is valid for a wide range of sample types. The procedure has been applied to a number of other rock standards of different types and also to some soils derived from parent materials ranging in composition from basic (olivine- gabbro) to acidic (granite). The results for a soil derived, for example, from olivine-gabbro, a parent material similar in composition to BCR-1, are shown in Table 111.For all of the samples analysed, the corrected results are reasonable, especially those for europium, which show marked consistency between different exposures. For gadolinium, the results are not entirely satisfactory and the correction equation for this element may have to be modified. The procedures outlined here for the elimination of molecular interference effects and for the standardisation of semi-quantitative SSMS values not only permit the direct determi- nation of the rare-earth elements in rocks and soils, but also have similar advantages for the SSMS technique in general, as applied to the analysis of non-conducting powders.127 May, 1976 ELWELL AWARD MEETING TABLE I11 COMPARISON OF SELECTED LITERATURE VALUES FOR BCR-1 WITH (1) SSMS VALUES AFTER CORRECTION FOR INTERFERENCE AND APPLICATION OF R S C S DERIVED FROM SYNTHETIC STAN- DARDS CORRECTED FOR INTERFERENCE AND (2) UNCORRECTED SSMS VALUES Contents of a soil (3) derived from an olivine-gabbro parent material similar to BCR-1 are also given. Results are expressed in parts per million. BCR-1 rock Soil, olivine-gabbro - I parent material, Liteiature Element value" Ce 53.9" Nd 29" La 23b Sm 6b Gd 6.6" Pr 7" DY 6.3" Yb 3.lb Er 3.6" Ho l b Eu 1.9" Tb 1.0" Lu 0.6" Tm 0.6" * a Ref. 1: b Ref. 2. SSMSt 45.8 33.8 31.4 10.8 10.2 9.9 4.8 2.3 1.9 3.2 2.2 0.9 0.9 (1) (5.7) ssMs : (2) 101 80 34 25 40 16 20 15 10 3.6 5.6 1.5 1.6 - S M S t (3) 40 39 36 11 (34) 9.6 6.9 2.1 0.9 3.5 1.5 0.2 0.8 - All results are averages of a t least two exposures, except that for Gd, which is a single value. References 1. 2. Flanagan, F. J., Geochim. Cosmochim. Acta, 1972, 37, 1189. Morrison, G. H., and Kashuba, A. T., Analyt. Chew., 1969, 41, 1842.

ISSN:0306-1396    

DOI:10.1039/AD9761300118

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

May, 1976 ELWELL AWARD MEETING 127 Elwell Award Meeting The following is a summary of the winning paper presented a t the Elwell Award Meeting of the Midlands Region held on January 20th, 1976. Molecular Emission Cavity Analysis of Some Phosphorus Compounds 0. Osibanjo Chemistvy Depavtment, Bivmingham Univevsity, P.O. Box 363, Bivmivzgharuz, B15 21’T The most common analytical method for the determination of phosphorus requires the con- version of phosphorus into orthophosphate ions, which react with molybdate ions to form 1 2-molybdophosphate ions that are determined co1orimetrically.l Flame-emission spectro- photometry offers the advantage of not requiring the pre-conversion of phosphorus into orthophosphate ions.Recent flame-photometric methods for the determination of phos- phorus rely on the measurement of the green emission derived from HPO molecules that are formed in a cool hydrogen-rich flame.The HPO emission is generated by phosphorus compounds when subjected to molecular emission cavity analysis (MECA) in a hydrogen - nitrogen flame. The MECA responses of a variety of organophosphorus compounds2 and metal phosphates have been investigated, using a modified flame spectrophotometer, as described previ~usly.~ The flame composition used was nitrogen 4.1 1 min-l, hydrogen 5.3 1 min-l and air 6.2 1 min-1.The cavities em-128 ELWELL AWARD MEETING PYOC. Analyt. Diu. Chem SOC. ployed in this study were made in 316 stainless-steel or aluminium cylinders, and had an optimum size of 8 mm diameter x 5 mm deep and a volume of 0.25 cm3.Organophosphorus Compounds For MECA, all of the organophosphorus compounds investigated gave the green HPO emission. For example, Belcher et al.3 found that the presence of hexane - propanol solvent (1 + 1) suppressed the MECA S, emission from diphenyl sulphide. This effect was eliminated by allowing the solvent to evaporate before inserting the cavity into the flame.Organic solvents were also found to suppress the MECA HPO emission from organophosphorus compounds but again the effect was eliminated by allowing the solvent to evaporate. The optimum solvent evaporation time was found to be 10 s for ethanol or benzene. After solvent evaporation linear calibration graphs were obtained for all 12 compounds investigated with the aluminium and stainless-steel cavities. Fig.1 shows the calibration graphs for some organophosphorus compounds using the aluminium cavity. All the com- pounds emit faster in aluminium cavities than in stainless-steel cavities and give enhanced sensitivities in the former, with enhancement factors of 3-20 fold. Solvent effects have previously been observed in MECA studies. I I I I I 0 10 20 30 40 Concentration of phosphorus, p.p.m.Fig. 1. Calibration graphs for some organophosphorus compounds using the aluminium cavity : A, triphenyl- phosphine ; B, tributyl phosphate ; C, triphenylphosphine oxide ; D, trimethylphosphite ; and E, triethylphosphite. The order of sensitivity of the groups of compounds in either aluminium or stainless-steel cavities is generally phosphine > phosphine oxide > phosphite > phosphate, the sensitivity thus increasing with decreasing oxygen content of the compounds.Detection limits of 0.1 p.p.m. of phosphorus were obtained for triphenylphosphine, tributylphosphine and tributyl phosphate. The coefficient of variation was 2-3% (10 results) for 10-15 ng of phosphorus for all compounds investigated. Because of the rapidity and sensitivity of the technique, it should have wide applications, for example in the determination of organophosphorus com- pounds in pesticides and in petroleum fractions.Effect of Cooling the Cavity first observed by Salet.4 The enhancement of HPO emission near a cool surface in a hydrogen diffusion flame was Enhanced S, emission was also observed when the MECA cavityillny , 1976 ELWELL AWARD MEETING 129 was water cooled,3 and therefore an investigation of the effect of water cooling of the cavity on the emission of the organophosphorus compounds was made.The effect of water flow- rate (and thus decreasing cavity surface temperature) on the emission characteristics of three of the compounds is shown in Fig. 2. The HPO emission from trimethyl phosphate is en- hanced by cooling the cavity, with the emission intensity remaining constant at water flow-rates above 5 ml s-l. Emission from diethyl phosphite is also enhanced by cooling, but greater cooling decreases the emission.The emission from di-(e-ethylhexyl) phosphate decreases and is eventually extinguished as the cooling of the cavity is increased. In general, it is the more volatile compounds that show enhanced emission. For such compounds, cooling can be used to enhance the sensitivity 2-6 times, and calibration graphs remain linear.Those compounds which are suppressed are less volatile; at higher cooling rates, these compounds are not volatilised in the cavity, and thus generate no emitting HPO species. Determination of Mixtures of Organophosphorus Compounds Because the t, value (time from initial cavity - flame contact to maximum emission) of each compound is characteristic of that compound under the experimental conditions ob- taining, it is possible to obtain resolved MECA peaks from compounds with sufficiently different t, values. Thus, mixtures of sulphur anions, such as sulphite and sulphate,5 and mixtures of organotin compounds, such as dibutyltin oxide and tributyltin oxide,6 give re- solved peaks and both components can be determined.The resolution of binary mixtures of organophosphorus compounds was achieved in an aluminium cavity. Fig. 3 shows the resolved peaks from a mixture of trimethyl phosphate (t, = 2.0s) and di-(2-ethylhexyl) phosphate (t, = 11.5 s). In general, a t, difference of 5 s is necessary under the present conditions to resolve peaks from nanogram amounts of organophosphorus compounds.When peaks are resolved, there is no effect of one compound on the peak height of the other compounds, and the calibration graphs coincide with those obtained for single substances. 0 1 2 3 4 5 6 7 Water flow-rate/ml s-' C A 0 10 20 30 Time/s Fig.2. Effect of water coolina on the MECA Fig. 3. MECA peaks from a mixture of (A) trimethyl phosphate (150 p.p.m.) and (B) di-(2-ethyl- hexyl) phosphate (40 p.p.m.). einisgion of some organophosphcks compounds. A, trimethyl phosphate ; B, diethylphosphate : and C, di-(2-ethylhexyl) phosphate. Attempts were made to separate three compounds: trimethyl phosphate (t, = 2.0 s), triphenyl phosphate (t, = 7.0 s) and di-(2-ethylhexyl) phosphate (t, = 11.5 s), but they were not completely successful.As was expected from the effect of cooling on the emission of the individual compounds, the response of trimethyl phosphate was enhanced, whereas those of the other compounds were extin- In this instance, water cooling was of assistance.130 ALTERNATIVES TO BIOLOGICAL METHODS Proc.Analyt. Div. Chem. SOC. guished when the cooling-water flow-rate was 10 ml s-1. When the water was turned off, the peaks for the two remaining compounds were obtained, only partially resolved as before. Inorganic Phosphates Metal phosphates and also orthophosphoric acid give rise to the characteristic HPO emis- sion in the MECA cavity. The alkali, alkaline earth and lanthanoid metal ions are parti- cularly effective in delaying and depressing MECA phosphate emission, just as they affect sulphate emission.5 The depressive effect of cations on sulphur anions emission in MECA has been circumvented by adding orthophosphoric acid to the analyte s~lution.~ Similarly, addition of an excess of sulphuric acid (0.3 M in the final solution) eliminates the depressive effect of cations on orthophosphate determination by MECA.An optimum-sized stainless- steel cavity lined with a silica cup5 was used. As the cationic interferences were readily removed, MECA was successfully applied to the rapid determination of phosphorus in ortho- phosphate rocks after fusion with sodium carbonate. The method has the advantage of speed of analysis and freedom from the silicon interference that is encountered in most spectrophotometric methods.The author thanks the Federal Government of Nigeria for the provision of a research scholar- ship and Professor R. Belcher and Drs. s. L, Bogdanski, L. Polo Diez and A. Townshend for their advice and encouragement. References 1. 2. 3. 4. 5. Burton, J. D., and Riley, J . P., Analyst, 1955, 80, 391. Belcher, R., Bogdanski, S. L., Osibanjo, O., and Townshend, A., Analytica Chivn. A d a , 1976, in Belcher, R., Bogdanski, S. L., and Townshend, A., Analytica Chiruz. Acta, 1973, 67, 1. Salet, G., C.R. Hebd. Se'anc. Acad. Sci., Paris, 1869, 68, 404; Bull. Soc. Chivn. FY., 1869, 11, 302; Belcher, R., Bogdanski, S. L., Knowles, D. J., and Townshend, A., Analytica Chivn. Acta, 1975, the press. Annln Phys., 1869, 137, 171. 79, 292. 6. 7. Akpofure, C. O., Belcher, R., Bogdanski, S. L., and Townshend, A, Analyt. Lett., 1975, 8, 921. Belcher, R., Bogdanski, S. L., Knowles, D. J., and Townshend, A., Analyticu Chivn. Acta, 1975, 77, 53.

ISSN:0306-1396    

DOI:10.1039/AD9761300127

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

130 ALTERNATIVES TO BIOLOGICAL METHODS Proc. Analyt. Div. Chem. SOC. Replacement of Biological Methods by Chemical and Physical Methods The following are summaries of three of the papers presented at a Meeting of the Analytical Division organised by the Joint Pharmaceutical Analysis Group and held on February 4th, 1976. Natural and Synthetic Peptides D. H. Calam National Institute f o v Biological Sfandavds and Contvol, Holly Hill, Lo?zdon, NM73 6RB Until a few years ago, peptides employed therapeutically were exclusively of natural origin and were considered t o be “biological products’’ incapable of complete characterisation by physical and chemical methods.This attitude was, and in some instances still is, reflected in their pharmacopoeia1 specifications, with emphasis on biological methods and monographs given only for formulations, and was dictated by inadequacies in methods of isolation and analysis.Control was exercised over manufacture through the Therapeutic Substances Regulations and over the final product by batch release, with submission of protocols including bioassay of the active component against a standard of similar composition.Determination of the structures of hormones, such as oxytocin and insulin, was followedMay, 1976 ALTERNATIVES TO BIOLOGICAL METHODS 131 in the late 1950s by developments of analytical techniques such as amino-acid analysis, thin-layer chromatography and gel filtration, and later by polyacrylamide gel electrophoresis. These methods revealed the homogeneity, or more often heterogeneity, of peptides from natural sources and indicated problems, such as co-crystallisation, which previously had not been recognised.For therapeutic use, synthetic peptides offer advantages of unlimited availability and freedom from certain active contaminants that are unavoidable in material of natural origin (vaso- pressin in oxytocin, T, and T, thyroid hormones in pork calcitonin) and possibilities of syn- thesis of active fragments or analogues with modified activity. Improvements in procedures, together with cleaner starting materials resulting from microbiological production of optically pure amino-acids, have led to more ambitious syntheses : molecules containing 30-40 amino- acid residues (relative molecular mass up to 5 000) are in commercial production, and those containing more than 100 residues have been prepared on a laboratory scale.As 10 g of a peptide for which the human dose is 100 pg represents 100 000 doses, one complex synthesis may provide sufficient material for many batches of formulated peptide. The criteria used to assess the quality of a synthetic peptide must provide evidence of molecular identity and composition as well as a quantitative assay.These criteria should be objective in the sense of being independent of knowledge of the route of synthesis, but the severity of acceptance limits may be subjective, depending on the molecular size and complexity of the product and on its intended use : the limits may well be significantly tighter for a large peptide or for one administered over prolonged periods.Examination of formulations is often complicated by the presence of a few micrograms of active peptide in 100-1000-fold excess of bulking agent, stabilisers, carrier or delay medium, many of which interfere with the chemical and physical examination of the drug substance, and some of which are themselves protein in nature. It seems reasonable, therefore, that the bulk peptide should be treated like any other drug substance and be the subject of a separate pharmacopoeial monograph, which may be much more detailed than one applicable only to a complex formulation.These factors can be illustrated with current BP and EP monographs for some natural and synthetic peptides. Oxytocin This small peptide is given on isolated occasions in small doses [%-lo pg (1-5 i.u.) per litre of dextrose infusion prepared from Injection containing 1-10 i.u.ml-l]. The monograph for Oxytocin Injection1 (a solution) is essentially unchanged from that in the BP 1968. It includes identification by a biological method, a limit test for vasopressor activity and a bioassay, but only one physical test for pH. There is no monograph for the bulk substance.The oxytocin available is now mainly synthetic and this monograph may appear incomplete. In fact, the biological tests are specific and sensitive: the uterine assay detects 1 ng (0.5 mu). Given the amount of peptide per vial, it would be difficult to replace the biological tests with chemical and physical tests. However, a valuable addition would be a test for total peptide in order to limit by-products of synthesis and storage, for example oxytocin dimer, which has a fraction of the activity (although more prolonged) of the monomer.This test, coupled with a maximum peptide content per unit of activity (as introduced for lypressin2) would go far to limit extraneous peptide. If the peptide content were determined by amino-acid analysis after hydrolysis and a nil limit on foreign amino-acids set, as with tetracosactrin, the vaso- pressor test, designed to control the level of vasopressin in preparations of natural oxytocin, would become unnecessary.There is increasing discussion about possible applications of radioimmunoassay for analytical purposes. It is worth noting that if the disulphide ring in oxytocin is opened with thioglycollate, radioimmunoassay measurements are unaffected although biological activity is totally destroyed : the test applied must have sufficient discri- mination to fulfil its intended use.Glucagon I t was one of the first natural peptides to be subject to pharmacopoeial requirements for the bulk s ~ b s t a n c e . ~ The monograph contains two identification tests, one biological and the other a crystallisation test in the presence of urea. Polyacrylamide gel electrophoresis, introduced Glucagon is about three times larger than oxytocin and about half the size of insulin.132 ALTERNATIVES TO BIOLOGICAL METHODS Proc.Analyt. Div. Chew. SOC. into the BP for the first time, is used to limit foreign pep tide^,^ including insulin, which is known to interfere clinically, and desamidoglucagon, a degradation product with 60% of the biological activity of the parent molecule.The limit applied to desamidoglucagon implies a lower limit of 92% for the biological activity, assuming that only glucagon is present, and can be compared with potency limits of 80-125y0 (fiducial limits 64-156y0) in the bioassay measuring increase in blood sugar in a minimum of 24 rabbits.There are also tests for light absorption, peptide content and zinc ; glucagon is obtained as a by-product in the purification of insulin and the zinc salt has more prolonged action than glucagon itself. By contrast with the monograph for oxytocin, this monograph includes physical and chemical methods which can be used to supplement and strengthen data furnished by biological methods.Glucagon Inj ection3 exemplifies another type of formulation : lyophilised peptide with lactose as a bulking agent and a separate vial of solvent. Polyacrylamide gel electrophoresis is again used for identification of glucagon and for the same limit test of desamidoglucagon as in the bulk. Lactose, identified as a reducing sugar, does not interfere in the electrophoretic tests, whereas gelatin, often present in delay formulations, prevents the use of such methods.The peptide content is measured by differential light absorption. Thus, some of the tests on the bulk substance are retained, some are altered and some replaced. The same bioassay is employed. Tetracosactrin Acetate Tetracosactrin is an active fragment of corticotrophin and, with a relative molecular mass of about 3 000, is the largest synthetic peptide currently subject to a BP m~nograph.~ It is identified by means of digestion with trypsin and separation of the products by a two-dimen- sional combination of thin-layer electrophoresis and chromatography.An authentic sample is treated in parallel. This method has high resolving power and discrimination and, in our hands, shows potential as a general pharmacopoeial method for identifying peptides. Other physical and chemical methods employed to assess the quality of tetracosactrin include : specific optical rotation, light absorption, determination of acetic acid by means of gas chromatography, quantitative amino-acid analysis after hydrolysis with a nil limit on foreign amino-acids, peptide content, a limit on foreign substances by electrophoresis on cellulose acetate, and a titrimetric limit on content of the sulphoxide oxidation product, which has reduced biological activity.Despite the information provided by these and other tests, the monograph is completed by inclusion of the standard test for abnormal toxicity in mice and a bioassay measuring steroidogenesis in isolated adrenal cells and setting a minimum potency on a mass basis.Thus, this monograph has a form intermediate between that for glucagon, des- cribed above, and that for pentagastrin,6 a much smaller synthetic analogue of gastrin, the physical and chemical control of which is believed to be adequate without recourse to a bioassay.Tetracosactrin Zinc Injection is a suspension designed to provide delayed release of the active peptide and the monograph7 for it has other novel features. The three main constituents, peptide, zinc and phosphate, are identified individually. The peptide is examined by cellulose acetate electrophoresis against a standard prepared in a similar solution, a method only possible because the delay medium does not interfere.The three constituents are determined by physical methods, i.e., atomic or light absorption, and there are further tests for pH and sedimentation rate. Nevertheless, two biological tests are included, an assay as for the bulk, and an in vivo test to demonstrate prolongation of action. I t is difficult to envisage non- biological procedures that could adequately replace the latter.Conclusions The criteria for assessment of quality and safety of a peptide should be applicable irrespective of its origin or intended use although the range of tests employed should take these factors into account : a product intended for repeated use as a delay preparation in a single individual might well need to be controlled more rigorously than one given as a diagnostic challenge test or a single injection.As more extensive and searching physical and chemical tests can be performed on bulk material, peptides should be treated as any other drug and pharmacopoeial monographs provided for the bulk substance as well as for particular formulations. Despite improvements in the resolution, sensitivity, specificity and accuracy of physical and chemicalMay, 1976 ALTERNATIVES m BIOLOGICAL METHODS 133 methods, a complete assessment of most peptides must continue to contain information pro- vided by biological methods.References 1, “European Pharmacopoeia, ’’ Volume 111, Maisonneuve, Sainte-Ruffine, 1975, p. 302. 2. “European Pharmacopoeia,” Volume 111, Maisonneuve, Sainte-Ruffine, 1975, p.260. 3. “British Pharmacopoeia 1973 Addendum 1975,” HM Stationery Office, London, 1975, p. 24. 4. Calam, D. H., and Storring, P. L., J . Biol. Stand., 1975, 3, 263. 5. “British Pharmacopoeia 1973,” HM Stationery Office, London, 1973, p. 465. 6. “British Pharmacopoeia 1973,” HM Stationery Office, London, 1973, p. 345. 7. “British Pharmacopocia 1973,” HM Stationery Office, London, 1973, p.467. Chemical Analysis of Vitamins A, D and E R. A. Wigg ins Defiartment of Industry, Labovatory of the Govevnment Chemist, Coviawall House, Stamford Street, London, SE1 9NQ Vitamins A, D and E do not comprise single entities but rather groups of structurally similar compounds which vary in their biological activity. Therefore, for a chemical method to give a true measure of biological activity it must be able to resolve and determine the isomers and analogues which constitute each vitamin.For this reason discussion is concentrated on the techniques of gas chromatography and high-performance liquid chromatography. Vitamin A activity includes : vitamin A, alcohol (retinol), its isomers and derivatives ; vitamin A, alcohol, its isomers and derivatives; and some carotenoids.The analysis of multivitamin preparations will usually involve determination of all-trans-retinol or one of its esters and possibly the most abundant isomer, 13-cis-retinol. The analysis of foodstuffs for vitamin A activity often requires the separation of carotenoids from retinol. Vitamin D activity normally only involves vitamin D, (ergocalciferol) or vitamin D, (cholecalciferol).Vitamin E comprises a group of eight compounds, the a-, p-, y- and 6-toco- pherols and the corresponding tocotrienols. The most common and biologically active member is a-tocopherol. Some vegetable oils contain sizeable proportions of the other toco- pherols and some tocotrienols. For example, soyabean oil contains SO?/, of a-, 6074 of y- and 20% of 6-tocophero1.l The analysis of the oil-soluble vitamins A, D and E is discussed by reference to the following general scheme : sample preparation and extraction ; chromatographic clean-up ; and detection and determination. Sample Preparation and Extraction Multivitamin preparations are usually oily solutions, tablets or capsules.The sampling of liquid preparations is straightforward.Tablets can be crushed in a ball mill and the powder sampled. Capsules can be slit open and the contents analysed or the whole capsule can be taken for analysis. It is preferable to carry out vitamin analyses on fresh foods but if this is not possible then freeze-drying provides a useful method for preserving foods for analysis. Vitamins A, D and E can be separated from foods, capsules and oily preparations by saponi- fication with ethanolic potassium hydroxide solution followed by ether extraction.Anti- oxidants such as ascorbic acid must be added to the saponification mixture unless the saponifi- cation is performed under nitrogen, a procedure which is particularly recommended for extraction of the tocopherols, which are easily oxidised in alkaline conditions.If the vitamins in tablet preparations are unprotected then direct extraction of the crushed tablets is possible. It is common, however, to protect the vitamins by gelatin encapsulation in which event the gelatin coating must be removed before solvent extraction. This can be done by warming the tablet powder with dilute ammonia solution or dimethyl sulphoxide a t 60 "C in a water-bath.Chromatographic Clean-up Partition chromatography is useful for the separation of retinol from vitamins D and E and the carotenoids. A useful system is partition between a mobile phase of 2,2,4-trimethyl- pentane and a stationary phase of methanol containing 10% of water; Sephadex LH 20 is Crown Copyright.134 ALTERNATIVES TO BIOLOGICAL METHODS Proc.Analyt. Div. Chem. SOG. used as the inert support for the stationary phase2 A combination of this partition system with chromatography on calcium hydrogen orthophosphate has been found necessary for the deter- mination of retinol in some foods, particularly offal. The calcium hydrogen orthophosphate is slurry-packed in hexane and the retinols eluted with diethyl ether in hexane.The progress of retinol and its derivatives can be followed during chromatography by observing the fluorescence at 350 nm with a low-power ultraviolet lamp. Thin-layer chromatography is a rapid way of separating vitamins D and E from sterols that interfere with their determination by gas chromatography. However, recovery of the vitamins from thin-layer plates can be difficult because of oxidation.The related technique of dry-column chromatography can provide a useful alternative to thin-layer chromatography. In this Laboratory, dry columns of alumina deactivated with 8% of water are used for clean-up prior to the determination of vitamin D by means of gas ~hroniatography.~ The vitamins r> are eluted with chloroform. An indicator dye is used that is known to elute with the vitamins D from the alumina dry columns.This facilitates the collection of the fractions containing vitamin D and avoids the necessity of calibrating the columns before use. For most foods and fish oils two successive alumina dry columns are necessary. The second column is the same as the first but before application of the extract the vitamins D are isomerised to the isotachy- sterols by treatment with a Lewis acid, e.g., antimony trichloride in chloroform.A problem in the analysis of multivitamin preparations for vitamin D can be the large amounts of a-tocopherol that are added. The procedure involving two columns of dry alumina has been found to provide sufficient clean-up for the analysis of 10 ,ug of vitamin D, or vitamin D, in the presence of 30 mg of K-tocopherol.Another method of removing excess of a-toco- pherol is to chromatograph extracts on alumina treated with orth~phosphate.~ Chromatography on columns of alumina deactivated with 10% of water slurry-packed in cyclohexane usually provides sufficient separation for the colorimetric determination of the tocopherol^.^ For the gas-chromatographic determination further purification is necessary in order to remove sterols, particularly cholesterol.A scheme for removal of cholesterol and other sterols includes precipitation from ethanol - water (72 + 28) followed by precipitation of digitonides and then passage through a column of Celite that has been impregnated with 6% digit onin .5 Detection and Determination Gas Chromatography Retinol and its esters decompose at the temperatures required for vaporisation on a gas chromatograph; however, retinol ethers are stable.6 Quantitative determination by means of gas chromatography of all-tvam-retinol and 13-cis-retinol is possible by conversion of the alcohols to the trimethylsilyl ethers.These two isomers are separated on 2-m columns of l"/d SE30 on Gas Chrom Q a t 175 "C.Squalane can be used as the internal standard.7 Fig. 1 shows the gas-chromatographic determination of vitamin A in a multivitamin tablet. There are two approaches to the gas-chromatographic determination of vitamin D, and vitamin D,. Vitamins D, and D, are thermally cyclised, at the temperatures required for vaporisation, to the pyro and isopyro isomers. The ratio of formation of these isomers is independent of sample size and operating temperatures* and can therefore be used for quanti- tative determination.The pyro and isopyro isomers of vitamins D, and D, can be resolved by using 2-m glass columns of 3% OV210 on Chromosorb W at 250 0C.9 An alternative approach is to convert the vitamins D, and D, to their isotachysterols before injection on to a gas chromatograph.The isotachysterols do not undergo thermal cyclisationlO and they can be separated on 2-m columns of 3% OV17 on Gas Chrom Q at 235 "C., Figs. 2 and 3 show gas-chromatographic determinations of vitamin D. For gas chromatographs fitted with a flame-ionisation detector the lower limit of sensitivity is about 100ng. If the lieptafluorobutyrates of the isotachysterols are prepared and an electron-capture detector used then the lower limit of sensitivity can be reduced to 10 ng.ll It is rare to encounter a sample in which both forms of vitamin D are present.This is to the advantage of the analyst as it means that vitamin D, can be used as the internal standard for the determination of vitamin D, and vice versa. As the two forms of vitamin D are chemically very similar it is usually possible to add the form of vitamin D that is to be the internal standard at the beginning of the analysis.May, 1976 ALTERNATIVES TO BIOLOGICAL METHODS 135 0 5 10 15 20 Time/rnin Fig.1. Multivitamin tablet. Gas-chromatographic assay of vitamin A. Packing, 1% SE30 on Gas Chrom Q; glass column, 2 m x 4 mm i.d. ; oven tempera- ture, 175 "C; sample size, 4 p g ; flame-ionisation detector.Both vitamins D in solution are in equilibrium with pre-vitamin D or precalciferol. At 20 "C the equilibrium mixture is 93% vitamin D, or D, and 7"/. pre-vitamin D, or When vitamin D is determined by means of gas chromatography it is the total vitamin D plus pre- vitamin D that is determined, as the pre-vitamins are thermally cyclised to the pyro and isopyro calciferols and are isomerised t o the isotachysterols by Lewis acids.lsotachystero 1-2 I sot ac h y st e ro 1-3 - 1 _ _ L I . - L Ti me/rni n 0 10 20 30 40 50 Fig. 2. Margarine. Gas-chroma- tographic assay of vitamin D. Packing, 3% O\'17 on Gas Chrom Q; glass column, 2 m x 4 mm id.; oven temperature, 235 "C; sample size, 100 ng; flame-ionisation de- tector.Ti rne/min Fig. 3. Multivitamin tablet. Gas-chromatographic assay of vitamin D. Packing, 3% OV17 on Gas Chrom Q; glass column, 2 m x 4 mm i.d. ; oven tempera- ture, 235 "C; sample size, 200 ng; flame-ionisation detector.136 ALTERNATIVES TO BIOLOGICAL METHODS YYOC. Analyt. Div. Chem. SOC. Two-metre columns of 3% OV17 on Gas Chrom Q at 235 "C can be used for the gas-chroniato- graphic analysis of tocopherols, using a-tocopherol propionate as the internal standard.The AOAC method for the analysis of pharmaceutical preparations for a-tocopherol and a-toco- pherol acetate recommends 5% SE30 on Gas Chrom P with dotriacontane as the internal standard.13 This resolution has been achieved by using 5-m columns of 0.5% Apiezon L on 110/120-mesh Anakron a t 235 OC.14 Alternatively the p- and y-tocopherols can be converted to their quinones, which can then be resolved on a binary mixture of the silicones SE52 and XE60 a t 220 O C .1 5 A problem in the analysis of pharmaceutical preparations for a-tocopherol can be the differentiation of d-a-tocopherol and dl-a-tocopherol because the rotation of d-a-tocopherol is small ([aID = 0.32').However, the optical rotation of the oxidation products of d-cc-toco- pherol after treatment with alkaline potassium hexacyanoferrate(II1) solution is [a],, = 26", whereas the products from racemic a-tocopherol have zero rotation. This increase in rotation makes the identification of enantiomers much easier.16 Neither of these columns will resolve the isomeric p- and y-tocopherols.High-performance Liquid Chromatography Reversed-phase partition chromatography on columns prepared from silica that has a chemically bound thin layer of a chlorosilane or a hydrocarbon has been used to separate retinol, retinol acetate, vitamin D, or D,, a-tocopherol, a-tocopherol acetate and a-tocopherol succinate. Methanol - water gradients at flow-rates of 1-2 ml min-l (1 000-1 500 p.s.i.) were used with l-m columns maintained at 50 "C. Vitamins D, and D, can be separated on 3-m columns of silica with an octadecyltrichlorosilane layer.A mobile phase of methanol - water (78 + 22) at a flow-rate of 0.7 ml min-l was used.17 Adsorption chromatography on microparticulate silica has been used to analyse pharma- ceutical preparations for vitamin D,.A 25-cm column was used with a mobile phase of 50% water-saturated heptane containing 0.4% ethyl acetate and 12y0 dichloromethane at a flow-rate of 0.6 ml min-l. 9-Nitrophenylacetonitrile was used as the internal standard.ls This system will not separate vitamins D, and D,. Pellicular column materials have been used for the quantitative analysis of all-trans-retinol acetate and 13-cis-retinol acetate.A mobile phase of hexane with 0.1% dioxane was used with ethyl benzoate as the internal standard.Ig The pellicular materials can be used to determine all-trans- and 13-cis-retinol in the presence of the corresponding acetate and propionate. A microparticulate silica gel adsorption column (25 cm) has been used to analyse shark-liver oil for retinol with a mobile phase of 30% hexane and 700/, dichloroethylene (50% water saturated).2o a, p, 6- and y-tocopherols and the corresponding tocotrienols have been separated on 2-m columns of 30-pm pellicular silica using a mobile phase of 0.5% of tetrahydrofuran in hexane.,l This system has been used to separate the tocopherols and tocotrienols of corn oil and wheat bran. The most suitable detector available at present for the analysis of vitamins A, D and E by high-performance liquid chromatography is the ultraviolet absorbance detector.Most literature reports have described the use of absorbance detectors with a 254-nm filter. Several fluorescence monitors are now commercially available and these could be useful for the analysis of vitamins A and E. This paper is published with the permission of the Government Chemist.References 1. Sebrell, jun., W. H., and Harris, R. S., Editors, "The Vitamins," Volume V, Second Edition, Academic 2. Bell, J. G., Chemy Ind., 1971, 201. 3. Bell, J. G., and Christie, A. A., Analyst, 1974, 99, 385. 4. Edlund, D. O., Filippini, F. A., and Datson, J. K., J . Ass. 08. Analyt. Chem. 1974, 57, 1OS9. 5.Christie, A. A., Dean, A. C., and Millburn, B. A., Analyst, 1973, 98, 161. 6. Dunagin, jun., P. E. and Olson, J. A., Analyt. Chew,., 1964, 36, 756. 7. Wiggins, R. A,, unpublished work. 8. Nair, P. P., Bucana, C., de Leon, S., and Turner, D. A., Analyt. Chem., 1965, 37, 631. 9. Edlund, D. O., and Anfinsen, J. R., J . Ass. Off. Analyt. Chem., 1970, 53, 287. Press, New York and London, 1972.10.11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 1976 ALTEKNATlVES TO BIOLOGICAL METHODS 137 Murray, T. I<., Day, K. C., and Kodieck, E., J . Chvomat., 1966, 98, 293. Wilson, P. W., Lawson, D. E. M., and Kodicek, E., J . Chvomat., 1969, 39, 75. Keverling Buisman, J. A.,, Hanewald, K. H., Mulder, F. J . , Roborgh, J. R., and I‘knning, K. J., “Official Methods of the Association of Official Analytical Chemists,” Twelfth Edition, Association Slover, H.T., Shelley, L. M., and Burks, T. L., J . Am. Oil Chem. SOG., 1967, 44, 161. Nair, 1’. P., Sarlos, I., and Machiz, J., Avchs. Biochem. Biophys., 1966, 114, 458. Ames, S. R., and Drury, E. E., J . A s s . Off. Analyt. Chem., 1975, 58, 58. Williams, R. C., Schmit, J . A., and Henry, R. A., J . Chvomat.Sci., 1972, 10, 494. Tomkins, I). F., and Tscherne, R. J., Analyt. Chem., 1974, 46, 1602. Vecchi, M., Vesely, J., and Oesterhelt, G., J . Chvomat., 1973, 83, 447. WiHiams, R. C., L>u Pont Liquid Chromat. DIeth. Bull., November 1973. Cavins, J . F., and Inglett, G. E., Ceveal Clzevn., 1974, 51, 605. T. Phavm. Sci., 1968, 51, 1326. of Official Analytical Chemists, Washington, D.C., 1975, p.836. Tetracyclines J. W. Lightbown Division of Antibiotics, National Institute fov Biological Standavds and Control, Holly Hill, Havnpstead, Lopzdon, NW3 6 R B A number of biological methods are used in the quality control of tetracyclines. In all instances the official assay is a determination of biological potency, while for certain tetra- cyclines the biological control of extrinsic toxicity is specified.For those tetracyclines administered by injection, control of pyrogenicity, freedom from hypotensive substances and sterility are examined by using biological methods. It seems likely that all of these aspects of quality, except perhaps one, will be measurable by chemical and physical methods in the fairly near future. Present legislation within the UK requires that all preparations of tetracycline and oxy- tetracycline, together with injectable forms of rolitetracycline and lyniecycline, should comply with the requirements of the Therapeutic Substances Regulations (TSR) in addition to those laid down in the European Pharmacopoeia (EP).Although the requirements of the TSR have been repealed, the conditions they have imposed continue to apply through Licenses of Right granted under the Medicines Act.Other tetracyclines, such as chlortetracycline, demeclo- cycline, doxycycline and methacycline are specified in the EP or British Pharmacopoeia (BP), while newer products, such as minocycline, are subject to control under the Medicines Act, on the lines laid down in the Compendium. The first TSR for aureomycin in 1953 followed the example of penicillin and streptomycin control and specified biological assay-without any alternative.The material was defined only as a yellow crystalline compound containing nitrogen and non-ionic chlorine. During the next 10 years a number of chemical assays were developed for penicillin and this resulted in pressure from the manufacturers for biological assay to be replaced by a chemical procedure.This led to the revised TSR of 1963, which allowed chemical or physical assay to be used for any preparation of an antibiotic providing that the Licensee was confident that it ensured that a given sample would comply with the required Minimum Biological Potency if tested. It clearly placed the responsibility on the manufacturer to ensure that his analytical procedures measured the content of a defined chemical substance which could be predicted to have the desired activity.The method of assay still had to be approved by the Licensing Authority. Little advantage was taken of this clause, even in relation to penicillin, until the specifications of the BP for penicillins were revised in 1968 to discard biological assay completely (in 1963 the biological assay went into small print).For tetracyclines it is only in the last 2 or 3 years that a number of licensed manufacturers have placed their trust in chemical assay. Early RP monographs for tetracycline, oxytetracycline and chlortetracycline included simple spectrophotometric assays of the substance “as is” or after treatment with acid or alkali, but the possible presence of epimers with unaltered spectral properties, and negligible biological activity, limited the value of this approach, particularly in relation to tetracycline. The description by Addison and Clark1 of a paper-chromatographic separation of epitetra- cvcline from tetracycline and other degradation products gave the basis of a more specific non-biological assay, but little advantage was taken of this.Two factors have probably138 ALTERNATIVES TO BIOLOGICAL METHODS Proc. Analyt. Div. Chenz. SOC. increased the interest in the development of a non-biological assay of tetracyclines in recent years : the comparatively high minimum potency specified for tetracycline and oxytetracycline, which was difficult to prove by biological assay as the need to show a lower fiducial limit greater than a potency equivalent to 9594 purity required an assay with a precision of the order of &2y0 ; and also, with the expiry of patents, interest in tetracycline assays spread to a number of laboratories that often did not possess biological expertise.The chemical assay for oxytetracycline described by Bailey2 was probably the first procedure to be used as a reliable replacement of biological assay for a tetracycline.A column separation on Celite with a hexane-ethyl acetate, pH3.3, buffer partition system was used. With practice it is reliable and has been shown to be so in a number of laboratories. High-performance liquid chromatography (HPLC) of oxytetracycline is being used successfully in the UK, in some laboratories, but no quantitative assay has been published.The development of pharmaceutical specifications for tetracycline has been influenced by the discovery of Benitz and Diermeier3 that one particular degradation product, epianhydro- tetracycline, had renal toxicity. The danger (which could not be demonstrated in a normal 24-h mouse test) was greatest in badly formulated products stored under adverse conditions and with the expiry of the patent on tetracycline the provisions of the TSR were extended in 1971 to include non-parenteral forms.Two years previously tests had been introduced into the BP to limit, by means of a thin-layer chromatographic test (TLC), the epianhydrotetra- cycline content of the parent substance and, by means of a spectrophotometric test, the con- tent in the dosage forms.The method has been found to be difficult to reproduce in some laboratories; it was replaced in the EP monograph by a modification which is a marked im- provement, although some laboratories still find it difficult. All of these methods appear to depend on a critical moisture content of the thin layer, which cannot be defined and to a certain extent must be determined by trial and error.More recently a number of HPLC systems have been described that allow the separation of tetracvcline and its impurities. These systems might well form the basis of a quantitative assay? but application to natural tetracycline mixtures, with a correlation of the quantitative determination of tetracycline and the biologically assayed potency, has not yet been reported.In the instance of oxytetracycline a good correlation between biological potency and oxytetra- cycline content obtained by the method of Bailey and by use of unpublished HPLC procedures has been obtained. With tetracycline a complication arises in the presence of up to 2.07, of chlortetracycline. Chlortetracycline is several times more active than tetracycline on a weight basis : with most assay organisms, the potency obtained biologically will therefore be expected to be higher than that obtained by HPLC and account must be taken of the chlortetracycline level in evaluating the correlation.Of the other tetracyclines, demeclocycline, chlortetracycline and minocycline have been assayed by a column method which is official in the US Code of Federal Regulations5 (with cyclohexane in place of benzene) specifying minocycline.The US Regulations also include LZ chemical assay for doxycycline involving paper-chromatographic separation with a pyridine - toluene, pH 4.2 buffer system. Elution of the separated bands irom the paper is followed by a spectrophotometric quantitative determination of the eluates. Both procedures involve comparison with a standard preparation processed as for the unknown.In both instances a minimum recovery of the standard is necessary for a valid assay: not less than 95% for the paper system and not less than 100 The method for minocycline has not proved satisfactory in our laboratories. In the early days, biological assay of antibiotics offered a high degree of specificity, but with the great increase in size of the tetracycline family this no longer applies and it is necessary to support the biological assay by reliable identification tests and also by tests to limit secondary tetracyclines. At present this is effected by a not very satisfactory TLC test described in the BP.Perhaps a reliable HPLC procedure could replace TLC for identification, and biological assay, in a single test.Of the other biological tests, toxicity control is already largely dependent on non-biological procedures in the one instance where toxicity, due to a known degradation product, is concerned, i.e., epianhydrotetracycline. An alternative to the biological mouse test is allowed under TSR.The safeguard against non-specific toxicity must lie in ensuring good pharmaceutical manufacturing practice and it is doubtful whether a non-specific animal toxicity test has a place in modern end-product specifications. 2y0 for the minocycline.May, 1976 EQUlPMENT NEWS 139 The test for histamine-like substances (as it was first known), now the hypotensive substances or depressor substances test, requires a minimum lowering of the blood pressure of a cat after injection of a specified dose of the antibiotic.This is the one test that it is difficult to imagine being replaced by a chemical or physical procedure. In more than 25 years we have never encountered a sample of a tetracycline, or any other antibiotic, which clearly failed to comply. In such a case it is difficult to devise a chemical or physical method to limit the unknown. In recent years there has been much interest in the “limulus test” which uses a lysate from the amoebocytes of the horse-shoe crab, Limulus polyphemzis, that is gelled by bacterial endotoxin. The test is used in some laboratories to screen water for injection for pyrogens, but as far as I am aware it has not been used successfully to replace the standard pyrogen test procedure for those tetracyclines that are injected. The only other biological test is that for sterility. Perhaps it might be thought that here is the one biological test which will never yield to the chemist, but I think already the possibility exists. All living organisms contain ATP in a fairly constant proportion (0.3-0.4% of cell C on a weight basis). Using the firefly luciferase enzyme system, which reacts with ATP with the emission of 1 photon of light for 1 molecule of ATP hydrolysed, and using a very sensitive photometer, it is claimed that as little as 0.1 pg of ATP can be measured. If one believes the claims it should be possible to detect from 10 to 100 organisms (1968) . 6 By using a combination of membrane filtration, low levels of contamina- tion would be demonstrated in a few minutes. Any organism should be demonstrated pro- vided that it is living, in contrast to traditional microbiological techniques, which will only detect the organisms appropriate to the media and temperature conditions of incubation. After death, ATP is dissipated. References 1. Addison, E., and Clark, K. G., .J. Phavwz. Phavmac., 1963, 15, 268. 2. Bailey, F., J . Phavm, Phavmac., 1969, 21, Suppl., 405. 3. Benitz, K. F., and Diermeier, H. F., Proc. Soc. Ex$. Biol. Aled., 1064, 115, 930. 4. Knox, J. H., and Jurand, J., J . Chromat, 1975, 110, 103. 5. Code of Federal Regulations, Title 21, Chapter 1, Part 446, Subpart A, Section 446.60 (b) (5). 6. Levin, G. V., Usdin, E., and Slonim, A. R., Aevospace Med., 1968, 39, 14.

ISSN:0306-1396    

DOI:10.1039/AD9761300130

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

May, 1976 EQUlPMENT NEWS 139 Equipment News Gas Chromatography A flame photometric detector system is available for the Hewlett-I’ackard Series 5830 and 5730 gas chromatographs. It can be fitted retro- spectively and is designed for such applications as monitoring environmental pollution and pesticide detection. In the detector the GC effluent is mixed with air, oxygen and hydrogen and is burned in a hydrogen-rich atmosphere in which the compounds of phosphorus and sul- phur are reduced.These compounds emit a characteristic light whose intensity is pro- portional to concentration and by using optical filters at 526 nm (for phosphorus) or 394 nm (for sulphur) a specific response is obtained. The transmitted light is detected by a photo- multiplier whose output is amplified by an electrometer.Hewlett-Packard Ltd., King Street Lane, Winnersh, Wokingham, Berks., RG11 5AR. Atomic Absorption A range of five “System Packs” for use with Sliandon spectrophotometers for atomic- absorption and fluorescence techniques is znnounced. Each pack consists of a selection of equipment to meet specific needs and results in considerable cost savings. Two of the packs offer the facility of using both the flamed-mode and flameless operation and with thc least expensive pack it is claimed that mercury and arsenic can be detcrmined clown to 2 and 5 parts per lo9, respectively.Shandon Southern Instruments Ltd., Cam- berley, Surrey. Microscopy A high-power microscope for fluorescence diag- nostic examinations with both transmitted and incident light excitation is announced.The FluorvaR uses an HB50 mercury-vapour lamp140 EQUIPMENT NEWS PYOC. Analyt. Div. Chem. SOC. and aspherical condenser with high aperture dry objectives and glycerine immersion obj ec- tives. Information on this and other VaR instruments is available in a new brochure. British American Optical Co. Ltd., 820 Yeovil Road, Slough, Bucks. There are nine alternative versions of the Olympus BH series of microscopes.Built from modular components they permit the assembly of microscopes to meet a wide range of specifica- tions. A. Gallenkamp & Co. Ltd., P.O. Box 290, Christopher Street, London, EC2P 2ER. Microcomputer A microcomputer which lies somewhere between the smaller minicomputer and the conventional microprocessor is announced.The PM16 Poly- nomialised Microcomputer system is suited to processing applications, in both analog and digital instrumentation, which require signific- ant mathematical treatment and involve equip- ment repetition quantities of from 1 to 300. Examples of applications are : analytical and control instrumentation for infrared spectros- copy, chromatography, meteorology, etc.; time- shared control of small process loops involving non-linear elements and simple sequence con- trol; and improving the accuracy of complex measurement systems involving multiple sen- sors, e.g., integrated mass flow. Digital Electronics, Bell & Howell Ltd., Electronics and Instruments Division, Lennox Road, Rasingstoke, Hants., RG22 4AW. Plasma Discharge Source Unit A 2-kW inductively coupled radiofrequency plasma discharge source unit from International Plasma Corporation is suitable for direct nebulisation of aqueous samples.The system operates a t low argon flow-rates and includes an impedance matching capacitor array. The source unit has a solid-state power supply and regulator circuitry and, used in conjunction with conventional single or multichannel emission spectrometers or spectrographs, permits detec- tion limits in the range 0.1-10 pg 1-1 for a wide range of elements.EDT Research, 65 Ivy Crescent, London, W4 5NG. Peak Height Detector The Labtech LT.lOO Peak Height Detector is available for automatic read-out from auto- analysis systems. The read-out can be either printer, teletype or a computer version and the results appear in true concentration form.There is a visual display for scaling and connec- tion to the analyser is either through a re- transmitting potentiometer or directly to the colorimeter. A logarithmic version is available €or AA.1 compatability. Frost Instruments Ltd., Fishponds Road, Wokingham, Rerks., RGll 2QA. Microwave Heaters A thermometer for measuring temperatures in microwave heaters is currently being patented.The thermometric fluid is xylene and it is claimed that temperatures can be determined within f 10% in the body of the sample while it is being bombarded with microwaves. Mercury Microwave Ovens, Wokingham, Berks. Gas Monitors A multipoint toxic-vapour area monitor designed for automatic sampling and measure- ment of ambient air is announced.The Wilks MIIIAN-201 uses a single wavelength infrared measurement system which permits a high degree of selectivity. It can be sensitised to monitor any one of over 300 toxic vapours at concentra- tions complying with OSHA and will sequenti- ally monitor up to 15 locations up to 400 f t away. A digital printer indicates concentra- tions in p.p.m., sample location and time of day.Wilks Scientific Corporation, P.O. Box 449, S. Norwalk, Connecticut 06856. Available in Great Britain from Techmation Ltd., 58 Edgware Way, Edgware, Middx., HA8 8 JP. Portable gas monitors, Models B/3007 and BZ/3007, can indicate the build-up of potentially explosive atmospheres of gases such as acety- lene, hydrogen and propane. They can be used for spot checking or for continuous monitoring for up to 50 h before battery re-charge or re- placement is necessary.The catalytic sensor is pulse operated and is said to detect flammable gases selectively and reliably over many years without the need for re-calibration. Fixed monitors for permanent installation are also available and BASEEFA Intrinsically Safe Certification for Division I areas is in accordance with SFA 3007 Gases Group IIC.Neotronics Ltd., Building 102, FSTS Site, Stansted Airport, Stansted, Essex, CM24 8QX.May, 1976 EQUIPMEKT NEWS 141 Dust Monitor A smoke density/dust monitor for use in ducts and chimneys of small- and medium-capacity industrial plant is announced. The M52081 is based on a comparative electro-optic technique using two beams of “white” light, a measuring beam through which the smoke or dust passes and a reference beam. This light is produced from a single beam which is split and caused to oscillate, resulting in two collimated beams.Dust or smoke content is determined by com- paring the light intensity of these reflected beams. The comparison is made by a photocell and amplifier, the measuring head producing a linear output signal of 4-20 mA, proportional to a selected measuring range of 0-100, 0-50, and 0-25% opacity.The measuring head can also be calibrated for a given concentration which, if exceeded, gives an alarm signal. The monitor is available in three sizes for applications where the maximum measuring distance does not exceed 2.5, 4.2 and 6.0 m. Siemens Ltd., Great West House, Great West Road, Brentford, Middx., TW8 9DG.Particle Size Analyser The “526” particle size micrometer and analyser is designed for the rapid optical sizing and counting of particles in the range 1.0-250pm. The double-image technique is used with a microscope which removes much of the tedium associated with particle sizing and counting. This cquipment can be used in air-pollution studies and a range of monitors and sampling equipment for use in this field is also available.Fleming Instruments Ltd., Caxton Way, Stevenage, Herts. pH Electrodes A new range of pH electrodes is offered by Intek. The storage cap of these electrodes has an absorbent liner soaked with buffer solution. This eliminates the need, when the electrode is not in use, for the conventional beaker of buffer solution, and facilitates storage.Another feature is a 10-15 MQ sensing bulb and non-plugging reference junctions, which substantially reduce resistance and result in a quicker response to pH changes. The electrode has an outer casing of high-im- pact inert polymer and is capable of withstand- ing four to five times the sensing bulb’s maximum working pressure of 150 lb in-2, which consider- ably reduces breakages.The same company offers a range of buffer powders in sealed sachets. Intek (UK) Ltd., 88 Brewery Road, London, N7 9ND. New Materials A water-soluble, vial-washing solution NE 555 Recycle is available for high-efficiency recycling of glass liquid-scintillation vials. Used in a machine it is claimed that washing and quality- control stages are integrated into one step, thus eliminating background recounts.Other bene- fits include surface protection of the vial against mechanical damage and preservation of optical surfaces. Nuclear Enterprises Ltd., Sighthill, Edin- burgh, EH 11 4EY. The Uni-Pore range of polycarbonate mem- branes is available in pore sizes from 0.015 to 8.0 pm with nominal thicknesses from 2 to 10 pm and diameters from 13 to 293 mm.They are superior to cellulosic membranes, being more uniform in pore geometry, stronger and more flexible. Bio-Rad Laboratories Ltd., 27 Homesdale Road, Bromley, Kent, RR2 9LY. Dry, regenerated cellulose membranes, which may be used to filter solvent systems such as esters, aldehydes and ketones, alcohols and amines and aqueous solvent systems, are avail- able.Pore sizes are 1.0, 0.6 and 0.2 pm and up to 142 mm in diameter. A range of plastic filter holders, including aerosol filters, is also announced. Anderman & Co. Ltd., Laboratory Supplies Office and Warehouse, Central Avenue, East Molesey, Surrey, KT8 OQZ. Literature The entire issue of Perkin-Elmer Analytical News, Number 12, is devoted to the discussion of Open Tubular Capillary Columns.Wall coated (WCOT) and porous layer (PLOT) are described together with their advantages in resolution and speed of analysis compared with packed columns. Perkin-Elmer Ltd., Post Office Lane, Beacons- field, Bucks., HP9 1QA. A 160-page tutorial handbook, the “LAB BASIC Programming Guide,” offers a complete self-teaching course to enable users to develop and run their own chromatography programmes on HP laboratory data systems.This hand- book can be ordered directly from Hewlett- Packard. Hewlett-Packard Ltd., King Street Lane, Winnersh, X70kingham, Berks., RGll 5AR.142 CORRESPONDENCE PYOC. Analyt. Diu. Chew. SOC. A new Sadtler Research Laboratories Inc. volume of nuclear magnetic resonance reference spectra in the collection of polymers has been published.These spectra will be of special interest to chemists using nmr spectroscopy in order to identify and characterise different types of polymers. The same company have published a new volume of infrared reference spectra in thc collection of adhesives and sealants. Heyden & Son Ltd., Spectrum House, Alderton Crescent, London, NW4 3XX. “Why X-Ray Spectrometry-Why Philips,” a 28-page booklet from Philips, describes typical analytical applications in a wide variety of industries and situations. X-Ray Analysis Dept., Philips Industries, Alinelo, Lelyweg 1, Eindhoven, The Nether- lands. A balance projection lamp chart, which lists lamps for all the leading makes of laboratory balances, has been prepared. Many manu- facturers have changed the types of projection lamps in the course of improvement and with the addition of new models, and the chart should enable users to identify quickly the specific model and lamp required, European Instruments, 80-82 Desborough Road, High Wycombe, Bucks, HPll 2PR. To accompany the single-beam SP6 series spectrophotometers two educational aids are now available-a full-colour wallchart and an introductory booklet on ultraviolet and visible spectrophotometry at L1 each. Pye Unicam Ltd., York Street, Cambridge, CB1 2PX.

ISSN:0306-1396    

DOI:10.1039/AD9761300139

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

142 CORRESPONDENCE PYOC. Analyt. Diu. Chem. SOC. Correspondence Correspondence is accepted on all matters of interest to analytical chemists. Letters should be addressed to the Editor, Proceedings of the Analytical Division, The Chemical Society, Burlington House, London, W1 V OBN. ‘Translation of “Elements of Experimental Chemistry’’ Sir, May I be allowed to correct an error in the article by K.Saito entitled “Analytical Chem- istry in Japan,” Proceedings, 1976, 13, 60? Saito states that YBan TJdagawa translated W. Henry’s “Elements of Experimental Chemistry” into Japanese, from the Dutch edition. In fact, the translation was from Henry’s earlier book “An Epitome of Chemistry.’’ This can be con- firmed by the fact that the first edition of “Elements of Experimental Chemistry” was not published until 1810, whereas the Dutch translation used by Udagawa was published in 1803 and must, therefore, be based on “An Epitome of Chemistry,’’ first published in 1801.I feel it is important that this error should now be corrected, since it has already appeared twice in earlier publications. 1*2 Readers of Professor Saito’s interesting article may wonder why Udagawa should choose to prepare a text-book, entitled, incidentally, “Semi Kaiso” (Foundations of Chemistry), from a Dutch translation of an English book.The reason is that, a t that time, Dutch was the only foreign language permitted by the Tokugawa Government and it so happened that the second edition (June 1801) of Henry’s “Epitome” was translated into German by J .B. Tronimsdorf (“Chemische Probirkabinet,” Erfurt, 1801). This, in turn, was translated and enlarged by A. Ypey into a Dutch version (“Chemie voor Beginnende Leifhebbers,” Amsterdam, 1803) and it was this version that was used by Udagawa. It is thus interesting to know that an English scientist was, albeit unwittingly, responsible for introducing chemistry into Japan ! References 1. 2. Tsuzuki, Y . , and Yamashita, A., .rap. Stud. Fujinsga, T., Talanta, 1972, 19, 385. Hist. Scz., 1965, 4, 41. Yours faithfully, C. J. Keattch Industvial and Laboratovy Sevvices, P.O. Box 9, Lyyne Regis, Dorset

ISSN:0306-1396    

DOI:10.1039/AD9761300142

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

May, 1976 CONFERENCES AND MEETINGS 143 Publications Received Cours de Chimie Analytique Genkrale. Tome IV. Exercices. M. Machtinger and R. Iiossett. Pp. vi + 284. Paris, New Uork, Barcelona and Milan : Masson. 1976. Price 75F. Nuclear Magnetic Resonance in Biochemis- try. Principles and Applications. Thomas I;. James. Pp. xiv + 413. Ncw York, San Francisco and London : Academic Press. 1975. Price $26.50.144 PUBLICATIONS RECEIVED Proc.Analyt. Div. Chewz. SOC. Interfacial Electrochemistry. An Experi- mental Approach. E. Gileadi, E. Kirowa-Eisner and J . Penciner. Pp. xviii + 525. London, Amsterdam, Don Mills (Ontario), Sydney and Tokyo : Addison- Wesley Publishing Company. 1975. Price L8.10. Wilson & Wilson’s Comprehensive Anal- ytical Chemistry. Volumc VI.Analytical Infrared Spectroscopy. Edited by G. Svehla. Pp. xiv +- 555. Amster- dam, Oxford and New York: Elsevier Scientific Publishing Company. 1976. Price llfl190; $7 G .50. Spectrophotometric Determination of Elements. Zygmunt Marczenko. Ellzs Horeelood Saries Z $ L Axalytical Cheinzstvy. Pp. xii + 643. Chich- ester : EI!is Horwood I k i i t e d . Distributed by John IVilev & Sons, Ncw Yoi-k, London, Sydney and Toronto.1976. Price d19.50; $42.90. Treatise on Analytical Chemistry. Part I. Theory and Practice. 1-olume 11. Edited by I. Ill. Kolthoff and l’iiilip J . Elving with the assistance of Ernest B. Santlell. Pp. xxvi -+ 6535-7232. New Yor-l;, London, Sycl- ney and Toronto: John Wilcy & Sons. 1975. Price L 2 2 ; $43.86. Aldehydes-Photometric Analysis.Vol- ume 3. Eugene Sawicki and Carole R. Sawicki. The Analysis of OYgavzic Matevials, Nzzvvlbev 9. Pp. xiv + 341. London, New York and San Francisco : Academic Press. 1976. Price L10.80; $26.75. Immobilized Enzyme Technology. Re- search and Applications. Edited by Howard H. Weetall and Shuichi Suzuki. Pp. x + 321. New York and London: Plenum Prcss. 1975. Price $30.Tagung Nukleare Analysenverfahren. Entwicklung Neuer Methoden. Dresden, DDR, Vom 12. Bis 16. MA1 1975. Edited by T. Braun and E. Bujdos6. Reprinted from the Journal of Radioanalytical Chemistry. Pp. 269. Budapest: Akadkmiai Kiad6. 1976. Price i13.90. Thermometric Titrations. J. Barthel. Cheinical Analysis, Voluwze 45. Pp. xiv + 209. New York, London, Sydney and Toronto: John Wiley & Sons.1975. Price L12.25; $24.55. Practical Pharmaceutical Chemistry. Third Edition. Part Two. -4. H. Beckett and J. 13. Stenlake. Pp. xii + 552. London : The Athlone Press. 1976. Price L15. Separation Methods in Biochemistry. Second Edition. C. J . 0. K. Morris and P. Morris. Pp. viii 4- 1045. London : Pitman Publishing. 1976. Price L32.50. Concise Etymological Dictionary of Chem- istry. Stanley C. Revan, S. John Gregg and Angela Rosseinsky. Pp. x + 140. London: Applied Science Publishers Obituary James Bernard We deeply regret 1976. Price i 7 . Att ri I I to announce the death on May loth, after a brief illness, of Mr. J . B. Attrill, Editor of -4nalytical Books and Mono- graphs a t the Chemical Society and former Editor of the Analyst in the period 1954-1973. A full obituary will appear in a later issue.

ISSN:0306-1396    

DOI:10.1039/AD976130143b

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

May, 1976 REPRINTS OF REVIEW PAPERS 145 Reprints of Review Papers Reprints of the following Review Papers published in The Analyst since 1965 are available from the Publications Sales Officer, The Chemical Society, Blackhorse Road, Letchworth, Herts., SG6 1HN (not through Trade Agents). The price per reprint is i l ; orders for six or more reprints of the same or different Reviews are subject to a discount of 26%.The appropriate remittance, made out to The Chemical Society, should accompany any order. “Activation Analysis,” by R. F. Coleman and T. B. Pierce (January, 1967). “Techniques in Gas Chromatography. Part I. Choice of Solid Supports,” by F. J . Palframan “Heterocyclic Azo Dyestuffs in Analytical Chemistry,” by R. G. Anderson and G. Nickless “Determination of Residues of Organophosphorus Pesticides in Food,” by D.C. Abbott and “Radioactive Tracer Methods in Inorganic Trace Analysis : Recent Advances, ” by J . W. “Gamma-activation Analysis,” by C. A. Baker (October, 1’36’7). “Precipitation from Homogeneous Solution,” by I?. E. S. Cartwright, E. J . Newman and “Industrial Gas Analysis,” by (the late) H. N. Wilson and G. M. S. Duff (December, 1967). “The Application of Atomic-absorption Spectrophotometry to the Analysis of Iron and “Inorganic Ion Exchange in Organic and Aqueous - Organic Solvents,” by G.J . Moody and “Radiometric Methods for the Determination of Fluorine,” by J . K. Foreman (June, 1969). “Techniques in Gas Chromatography. Developments in the van Deemter Rate Theory of Column Performance,” by E.A. Walker and J. F. Palframan (August, 1969). “Techniques in Gas Chromatography. Choice of Detectors,” by T. A. Gough and E. A. Walker (January, 1970). “Laser Raman Spectroscopy,” by P. J . Hendra and C. J . Vear (April, 1970). “Ion-selective Membrane Electrodes,” by Ern0 Pungor and KlAra T6th (July, 1970). “X-ray Fluorescence Analysis,” by K. G. Carr-Brion and K. W. Payne (December, 1970).“Mass Spectrometry for the Analysis of Organic Compounds,” by A. E. Williams and H. E “The Application of Non-flame Atom Cells in Atomic-absorption and Atomic-fluorescence “Liquid Scintillation Counting as an Analytical Tool,” by J . A. B. Gibson and A. E. Lally “The Determination of Some 1,4-Benzodiazepines and Their Metabolites in Body Fluids,” “Atomic-fluorescence Spectrometry as an Analytical Technique,” by R.F. Browner (October, 1974). “The Use of Precipitate Based Silicone Rubber Ion-selective Electrodes and Silicone Rubber Based Graphite Voltammetric Electrodes in Continuous Analysis, ” by 2s. FCher, G. Nagy, I<. Tbth and E. Pungor (November, 1974). “The Examination of Meat Products with Special Reference to the Assessment of the Meat Content,” by D.Pearson (February, 1975). “Cherniluminescence in Gas Analysis and Flame-emission Spectrophotometry, ” by J . H. Glover (July, 1975). “The Analytical Role of Ion-selective and Gas-sensing Electrodes in Enzymology,” by G. J . Moody and J. D. R. Thomas (September, 1975). “Thiazolylazo Dyes and Their Applications in Analytical Chemistry, ” by H%vard R. Hovind (November, 1975).“Sample Preparation in the Micro-determination of Organic Compounds in Plasma or Urine,” by Eric Reid (January, 1976). “Recent Advances in the Ring Oven Technique,” by Herbert Weisz (March, 1976). “The Radioimmunoassay of Drugs,” by J . Landon and A. C. Moffat (April, 1976). “Analysis and Assay of Polyene Antifungal Antibiotics,” by A. H. Thomas (May, 1976). and E. A. Walker (February, 1967). (April, 1967). H. Egan (August, 1967). McMillan (September, 1967). D. W. Wilson (November, 1967). Steel,” by P. H. Scholes (April, 1968). J . D. R. Thomas (September, 1968). Part 11. Part 111. Stagg (January, 1971). Spectroscopy, ” by G. F. Kirkbright (September, 197 1). (October, 1971). by J. M. Clifford and W. Franklin Smyth (May, 1974).

ISSN:0306-1396    

DOI:10.1039/AD9761300145

出版商:RSC    

年代:1976

数据来源: RSC