摘要:

Proceedinas .Cof the Analytical Division ofThe Chemical SocietyCONTENTS351 1975 CS Award for ChemicalAnalysis and Instrumentation351 Analytical Chemistry in WestGermany352 Summaries of Papers352 'Analytical Chemistry ofDrug Metabolites'359 'Research and Development Topicsin Analytical Chemistry'361 Equipment News363 Analytical Chemistry Trust Fund364 Conferences and Meetings365 Publications Received368 Analytical Division DiaryVolume 13 No 12 Pages 351 -368 December 197PADSDZ 13(12)351-368(1976)ISSN 0306-1396December 1976PROCEEDINGSOF THEANALYTICAL DIVISION OF THE CHEMICAL SOCIETYOfficers of the Analytical Divisionof the Chemical SocietyPresidentD. W. WilsonHon. SecretaryP. G. W. CobbSecretaryMiss P. E. HutchinsonHon. TreasurerJ.K . ForemanHon. Assistant SecretariesD. 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 a1combined subscription with The Analystand Analytical Abstracts.@ The Chemical Society 1976Offici a I,Standardised andRecommendedMethods of AnalysisSECOND EDITION (1 973)Compiled and Edited forTHE ANALYTICAL METHODS COMMITTEEofbyThe Society for Analytical ChemistryN. W. Hanson, BSc, PhD, FRICPp. xxiv + 897 f17.00; U.S. $42.50ISBN 0 85990 704 XObtainable from The Publications Sales Officer,The Chemical Society, Blackhorse Road, Letchworth, Herts., SG6 1 HNMembers of the Chemical Society are entitled t o buy one copy fortheir own personal use at the special price of f 14.50 (U.S. $36.50)provided they order direct and enclose remittance

ISSN:0306-1396    

DOI:10.1039/AD97613FX041

出版商:RSC    

年代:1976

数据来源: RSC

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Analytical Division DiaryJANUARYThursday, 6th, 11 a.m.: SheffieldAtomic Spectroscopy Group, the Board of theAnnual Reports on Analytical AtomicSpectroscopy and the Modern Methods ofAnalysis Group of the Sheffield Metal-lurgical and Engineering Association :Fourth Annual Reports on AnalyticalAtomic Spectroscopy Symposium.“The State of Noise Studies in AnalyticalSpectroscopy,” by Professor V. G. Mossotti.“Background Correction Using the ZeemanEffect,” by J. B. Dawson and E. Grassam.“Determination of Nitrogen in Waters Usingthe ICP,” by G. F. Kirkbright and A. Gunn.“Determination of Trace Elements in MetalsUsing AAS and an Induction Furnace,”by J. R. Headridge and D. Andrew.“The Development of a Dedicated AASpectrometer, Using an Electrically HeatedTube Furnace, for the Determination ofElements Forming Volatile Hydrides, andthe Application of the Technique to SomeIndustrial Problems,” by C.W. Fuller andJ. R. F. Broughton.lianmoor House, The University, Shore Lane,S heffield .Wednesday, 12th, 6.30 p.m. : LondonMicvochemical Methods and Special TechniquesDiscussion on “Head Space Analysis,” to beThe Savoy Tavern, Savoy Street, London,Groups.introduced by A. R. Jeffs.W.C.2.Thursday, 13th, 4 p.m.: GlasgowScottish Region, jointly with the Glasgow andWest of Scotland Section of the CS and theAndersonian Chemical Society.“Profits and Prophets,” by Professor J.Hawthorn.Room C133, Chemistry Department, Univer-sity of Strathclyde, Cathedral Street,Tuesday, 18th, 6.30 p.m.: BirminghamMidlands Region.“A Polarographic and Coulometric Study ofthe Iron(II1) - Solochrome Violet RS Sys-tem,” by J. E. Lewis.“The Determination of Nitrogen-containingCompounds by MECA,” by A. Calokerinos.“Application of a New Polymer Network forAnalytical Gel-permeation Chromato-graphy,” by A. W. J. Brough.Lecture Theatre 101, Haworth Building, TheUniversity, Birmingham.Friday, 21st, 6.30 p.m.: SalfordNorth West Region : Annual General Meeting,followed by the Address of the retiringChairman.“Analysts or Analytical Scientists,” by L. S.Bark.Theatre 3, Chapman Building, The University.Salford.Friday, 21st, 6 p.m.: BristolWestevn Region : Annual General Meeting.School of Chemistry, The University, Bristol.“MECA,” by A. Townshend.Tuesday, 25th : LondonSouth East Region : Annual General Meeting,6 p.m.Micvochemical Methods Group : Annual Gene-ral Meeting, 6.15 p.m., followed by aJoint Meeting, 6.30 p.m.“Opium-Analysis and Anecdotes,” by C. AJohnson.Linnean Society, Burlington House, PiccadillLondon, W.l.Wednesday, 26th, 7.15 .p.m. : ThornabyNovth East Region : Annual General Meeting.Discussion on “Analytical Chemistry in theNorth East, Past, Present and Future,”to be introduced by R. C. Chirnside.Glasgow . Golden Eagle Hotel , Thornaby, Cleveland.Printed by Heffers Printers Ltd Cambridge Englan

ISSN:0306-1396    

DOI:10.1039/AD97613BX043

出版商:RSC    

年代:1976

数据来源: RSC

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Vol. 13 No. 12 December 1976 Proceedings of the Analytical Division of the Chemical Society 1975 CS Award for Chemical Analysis and Instrumentation The third of these CS Awards, sponsored by Perkin-Elmer Ltd., has been made to Professor T. S. West, Director of the Macaulay Institute for Soil Research, Aberdeen, for his contribu- tions to chemical analysis and the development of techniques and of physico-chemical instru- mentation.In the former area he has made major con- tributions with his research students, while at the University of Birmingham, to the application of clielating agents related to ethylenediamine- tetraacetic acid and to the development of complexometric indicators based on bishydroxy- azo dyes and trishydroxybisazo compounds, such as Acid Alizarin Black SN, and various dicarboxymethylaminomethyl-substituted an- thraquinones.Various highly selective spectro- photometric reagents for trace metals such as calcium, beryllium, copper and silver and for anions such as sulphide and cyanide were evolved, as well as the specific lanthanide- alizarin - complexone (alizarin fluorine blue) ternary complex system for fluoride ion.Work was also done on the evolution of ultra-micro techniques for elemental and functional-group analysis of organic compounds. Similarly, in the area of instrumentation, while a t Imperial College, West pioneered with his students the techniques of flame atomic- fluorescence spectroscopy and electrothermal atomisation by the carbon-filament device, the use of piezoelectric crystal detectors for atmos- pheric pollutants and microwave-excited elec- trodeless discharge lamps as line sources, etc.Professor T . S. West (R) Yeceives the medal from Pvofessov C . C. A d d i s o n , Pvesident of T h e Chemical Society. I n addition he continued work on chelating agents for molecular-absorption and fluorescence spectroscopy, on solvent-extraction separation techniques and ternary-complex formation, and he undertook exploratory work on photo- chromism and absorption - fluorescence phenomena, for organic and inorganic compounds, in diffusion layers a t electrode surfaces under conditions of low current densities. 351

ISSN:0306-1396    

DOI:10.1039/AD976130351a

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

352 ANALYTICAL CHEMISTRY OF DRUG METABOLITES Proc. AnaZyt. Div. Chern. SOC. Analytical Chemistry of Drug Metabolites The following are summaries of the four papers presented at a Joint Meeting of the Chromato- graphy and Electrophoresis Group with the Midlands Region held on May ZBth, 1976, at the Loughborough University of Technology. Analytical Problems Involved in the Metabolism of Drugs and Foreign Compounds J.W. Gorrod Department of Pharmacy, Chelsea College, Manvesa Road, London, S W3 6LX During the transit of a xenobiotic through a biological system, it is usually subjected to bio- transformation reactions to yield highly polar, water-soluble metabolites. In many instances, these ultimate metabolites are relatively stable and provided they are not subjected to ex- tremes of either pH or temperature their analysis is associated only with problems of extract- ability into an organic phase, when this is required.However, as knowledge on the mechanism of formation of these metabolites has become available, it has been increasingly apparent that many intermediates in drug metabolism reactions are highly reactive or unstable species and their analysis often presents problems.These problems are considered below under the metabolic reactions involved. Problems Due to Metabolic Attack on Carbon Atoms Epoxide Formation formation. or react with nucleophiles such as glutathione. Metabolism of either aromatic or aliphatic double bonds can initially involve epoxide Aryl epoxides can spontaneously isomerise to phenols, hydrate to dihydrodiols The last two reactions produce unstableDecember, 1976 ANALYTICAL CHEMISTRY OF DRUG METABOLITES 353 products that decompose, depending on the reaction conditions, to various compounds.As the propensity for a molecule to react via a certain pathway depends on the nature of the bond affected, it is apparent that problems can arise when comparing not only different molecules but even different sites of oxidation within the same molecule.Dealkylation Metabolic attack on an a-carbon atom adjacent to a hetero-atom leads to the formation of unstable carbinols, which usually break down spontaneously to give the dealkylated com- pound and the corresponding aldehyde. If stabilisation of the hetero-atom - carbon atom bond occurs, then the corresponding a-hydroxy products may be found but as they are relatively unstable they may cause problems in analysis.Hydroxylated compounds formed by metabolic attack on an a-carbon atom adjacent to a nitrogen atom may be highly reactive and able to form cyclic compounds or to dehydrate. As these reactions are often pH dependent, artifacts can be produced owing to changes in the environment of the molecules during work-up procedures.Deamination Metabolic attack on an a-carbon atom in an aliphatic amine produces an a-carbinolamine, which breaks down spontaneously to give the corresponding aldehyde (or ketone) and ammonia. As ketones may be formed via the breakdown of certain other metabolites of aliphatic amines (see Aliphatic N-Hydroxylation), their formation should be interpreted with caution.Problems Due to Metabolic Attack on Nitrogen Atoms Aliphatic N-Hydroxylation alkali and air produce oximes. environment. This reaction yields metabolites that are particularly unstable and in the presence of Oximes can then readily hydrolyse to ketones in an acid Aromatic N-Hydroxylation Compounds are produced that rearrange in the presence of hydrochloric acid to amino- phenols and chloroanilines. Arylhydroxylamines are easily oxidised to nitroso compounds and may disproportionate into amino and nitro compounds.Amide N-Hydroxylation to give the corresponding o-amidophenol. to derivatise these compounds with alkylating or acylating agents. This reaction gives hydroxamic acids, which can rearrange either enzymically or chemically This reaction is enhanced if attempts are made Tertiary Amine N-Oxidation lated product.that may rearrange or undergo elimination reactions very efficiently. Amine oxides are produced, which can undergo elimination reactions to yield the dealky- Amine oxides also react with acylating agents to give reactive intermediates Problems Due to Metabolic Attack on Sulphur Atoms Sulphoxidation is known to occur metabolically and to require NADPH, and oxygen.However, as this reaction occurs non-enzymically in the presence of trace metals, copper in particular, problems may again arise. In addition to the above specific problems, the general problems associated with storage of any chemical in a biological environment are obvious. Biological fluids contain hydrolytic enzymes, which may release compounds from their conjugates and thereby give misleading results.Biological fluids also contain myriad organic compounds that may react with drug metabolites to yield artifacts. However, provided it is realised that metabolites are not formed or excreted in an inert environment, nor are they chemically inert, then steps can be taken to overcome many of these problems.354 Use of Thin-layer Chromatography in the Quantitative Analysis of Drugs and Metabolites in Body Fluids ANALYTICAL CHEMISTRY OF DRUG METABOLITES Proc.Analyt. Div. Chem. SOC. D. A. Stopher Pfizer Centval Research, Ramsgate Road, Sandwich, Kent In the analytical chemistry of drug metabolites, quantitative thin-layer chromatography has not been used as widely as other methods, such as gas chromatography.There are a number of advantages in using thin-layer chromatography ; many modern drugs are thermally unstable and so not amenable to gas chromatography, the technique is relatively easy to handle; and a thin-layer plate can accept heavy loadings of relatively crude extracts of plasma. Thin-layer chromatography can provide a quickly developed assay that can be used for drugs administered to animals in toxicity trials and also assays of greater sensitivity when the drug is given in therapeutic doses to man.The conditions for the preparation of thin-layer plates must be carefully controlled in order to obtain reproducible results. Major errors in the quantitative application of solvents to thin-layer plates arise from “creep-back” of solution on to the syringe needle.This effect can be overcome by the use of PTFE-coated needles. Methods of application of the sample have been studied by Brain and Turner.l They concluded that each analyst should carefully check the personal errors involved when using their own experimental conditions. A compound can be determined on thin-layer plates by direct absorption in the visible or ultraviolet regions of the spectrum, by fluorescence quenching of a fluorescent substance incorporated into the absorbent layer, by fluorescence emission or by phosphorescence of the compound or a derivative. As an example of direct absorbance, Garceau et aZ.2 developed an assay for primidone and two metabolites in plasma and urine.The sensitivity of the assay was about 1 pg ml-1 and all three compounds could be determined simultaneously in extracts of urine. Many compounds that do not absorb strongly in the ultraviolet or visible regions of the spectrum can be converted into derivatives for quantitative densitometry. A sensitive assay for imipramine and its metabolite desmethylimipramine in plasma was developed by Nagy and Treiber.3 After development, the plate was exposed to nitrous gases, which gave an intense yellow colour with these compounds.Densitometry was carried out at 405 nm and a sensitivity of 5 ng ml-1 in plasma was reported. Smith et aL4 developed an assay for apocodeine and its metabolites aponiorphiiie and nora- pornorphine in rat urine using fluorescence quenching.Atmospheric oxidation of the meta- bolites on the thin-layer plate produced an increase in the fluorescence quenching eff ect with time. Fluorescence quenching has also been used for the assay of a Pfizer cerebral vasodilator compound, UK-12130, and its demethylated metabolite in urine and plasma. UK-12130 U K - 12130 Metabolite and its metabolite were extracted with ethyl acetate and the concentrated extract was applied to the plate.After chromatography, both compounds could be determined on the plate. The sensitivity was about 1 pg d-1 and the standard graph was linear from 1 to The use of fluorescence emission can give much greater sensitivity than either direct absorbance or fluorescence quenching. A variety of reagents have been used to introduce fluorescent groups.Dansyl chloride has been used to give a highly sensitive method for the determination of biogenic amines.5 Fluorescarnine is a useful fluorigenic reagent for primary amines.6 As the reagent is not itself fluorescent, it can be sprayed on to the thin-layer plate after development. 10 pg ml-l.Decembev, 1976 ANALYTICAL CHEMISTRY OF DRUG METABOLITES 355 De Silva et aZ.7 developed a thin-layer chromatographic assay for flurazepam afid its major metabolites in blood.These compounds were converted into benzophenones and then treated with dimethylformamide to give the highly fluorescent 9-acridanones. These were separated by thin-layer chromatography and determined on the plate. The limits of detection were 0.5-1.0 ng ml-l of each compound in blood.A Pfizer P-blocking drug, tolamolol, was assayed in plasma by formation of a fluorescent derivative with the reagent 1 -e t hoxy-4- (dic hloro- 1,3,5-t riazin yl) napht halene .8 An internal OH I CONHz a:I3H 2.C H. C H 2N H C H 2C H 2 0 Tolamolol standard was used and the sensitivity was 2 ng ml-1 of tolamolol in plasma. References 1. 2 . 3. 4. 5 . 6. 7. 8. Brain, K. K., and Turner, T.D., J . Chromat., 1971, 61, 157. Garceau, Y., Philopoulos, Y., and Hasegawa, J., J . Pharm. Sci., 1973, 62, 2032. Nagy, A., and Treiber, L., J . Phavm. Pharmac., 1973, 25, 599. Smith, R. V., Cook, M. R., and Stocklinski, A. W., J . Chromat., 1973, 87, 294. Seiler, N., J . Chromat., 1971, 63, 97. De Silva, J. A. F., and Strojny, N., Analyt. Chem., 1975, 47, 714.De Silva, J. A. F., Bekersky, I., and Puglisi, C. V., J . Pharm. Sci., 1974, 63, 1837. Stopher, D. A., J . Pharm. Pharmac., 1975, 27, 133. Gas - Liquid Chromatographic Methods for the Analysis of Drugs and Their Metabolites A. C. Moffat Home O@ce Central Research Establishment, Aldermaston, Berkshire, RG7 4PN Drugs and their metabolites are often difficult to analyse by gas - liquid chromatography because of their polarity.In general, the metabolites are more polar than the parent drug, so that the metabolites tend to have longer retention times and asymmetric peak shapes. The order of polarity is ethers < esters < aldehydes and ketones < alcohols < amines < phenols < carboxylic acids, and the problems associated with gas - liquid chrom- atographic analyses increase in the same order.Extraction of the biological material at a number of different pH values or with different solvents can yield an initial chemical separation that is useful for identifying the metabolites. Conjugated metabolites can be hydrolysed to the original metabolite and then re-extracted, while quaternary ammonium compounds can be extracted by ion-pair techniques.Sample preparation is all-important in order to minimise any decomposition of the metabolite by acids, alkalis, oxygen or light. The column and conditions of use should give adequate separation of drug and metabolites from each other and from co-extracted biological materials, with good peak shapes for quanti- tation. Drugs such as N-oxides or hydroxylamines may decompose in the injection port,l and this fact must be recognised if an accurate metabolic profile is to be obtained.On the other hand, the decomposition of quaternary ammonium compounds such as thiazinamium to their tertiary analogues does allow their analysis by gas - liquid chromatography.2 Packed columns are normally used, although the use of open-tubular capillary columns with efficiencies of greater than 10 090 plates is increasing.Ideally, the column should be of glass and silanised before use. Supports should be acid washed and DMCS treated in order to remove active sites, (e.g., Chromosorb G or Supelcoport). In addition, the support can be treated with polymer acids or potassium hydroxide for the chromatography of free acids and bases, respectively.356 ANALYTICAL CHEMISTRY OF DRUG METABOLITES Proc.AnaZyt. Div. Chem. SOC. The stationary phases in common use are listed in Table I together with their McReynolds constants3 and maximum operating temperatures. An increase in polarity will normally give a greater degree of separation of polar materials, but at the expense of a lower maximum operating temperature.However, the new polar silicone stationary phases such as SP-2300, Silar 1OC and OV-275 (McReynolds constants of 2 408,3 682 and 4 219, respectively) can be used up to 250 "C and their use is increasing. In general, a thermostable low-loaded column such as 2-3% SE-30 or OV-17 is the column of choice for an initial screen for the presence of metabolites extracted from a biological medium.Temperature programming will ensure that the column is used to its maximum advantage. TABLE I STATIONARY PHASES COMMONLY USED IN DRUG METABOLISM STUDIES Maximum McReynolds operating Stationary phase constant temperature/"C Apiezon L .. .. . . SE-30 .. .. . . OV-17 .. .. . . QF-1 .. .. .. XE-60 .. .. . . Cyclohexane dimethanol succinate . . Carbowax 20M . . .. . . Diethylene glycol succinate ..143 217 884 1 500 1785 2 017 2 308 3 555 300 300 300 250 250 230 230 190 Many metabolites of drugs can be successfully co-chromatographed with the parent drug, provided that the metabolite is neither too polar nor decomposes on the column. Alter- natively, a derivative can be made which often (a) is more volatile, (b) is more thermostable, (c) gives a better peak shape, (d) enhances separation, (e) increases sensitivity of detection, e.g., in conjunction with an electron-capture detector, (f) permits the separation of optical isomers by the formation of diastereoisomers, or (g) enables some functional-group analysis to be performed.However, the preparation of derivatives is never a substitute for the use of good columns. Derivatisation has been recently reviewed4p5 and the more useful methods are listed below according to the functional groups concerned.Esters can be reduced to the alcohol with aluminium lithium hydride for later derivatisation by an electron-capturing agent. Alcohols can be converted into methyl ethers with methyl iodide and dry silver oxide or into trimethylsilyl ethers with BSA, BSTFA or TMSI.For electron-capture work, chloromethyl- dimethylchlorosilane or its bromine or iodine homologues are used. Acylation is discussed under secondary amines. Quaternary ammonium compounds have been reduced to the tertiary amine with sodium borohydride. Alternatively, they can be converted into the tertiary analogue2 directly in the injection port. Tertiary amines normally chromatograph well, but when the use of an electron-capture detector is required, pentachlorobenzyl chloroformate will form carbamates, which can be chromatographed directly, or the carbamate can be hydrolysed to the secondary amine and then made to react as below. Amitriptyline derivatives can be converted into anthraquirione with an oxidising agent6 or into a hydrocarbon by a Hofmann exhaustive methylation and degradation.' Secondary amines are acylated easily with the appropriate acid chloride or anhydride in the injection port of the chromatograph.Trifluoroacetyl and heptafluorobutyryl derivatives are the most popular for electron-capture detector work, while [14C]acetyl chloride has been used for radioactive detection methods. Diastereoisomers of enantiomorphs can be pre- pared by using trifluoroacetyl L-prolyl chloride or (+ ) -mandelyl chloride.Primary amines can be converted into Schiff bases with aldehydes or ketorles, or into iso- thiocyanates with carbon disulphide, as well as being acylated. Carboxylic acids are normally esterified. Methyl esters are the most popular and can be easily formed with diazomethane solution or by co-injection of trimethylanilinium hydroxide in the injection port.December, 1976 ANALYTICAL CHEMISTRY OF DRUG METABOLITES 357 Barbiturates can also be methylated in a similar manner, or butylated with tetrabutyl- ammonium hydroxide in order to differentiate N-demethylated metabolites from the parent barbiturate .Carbamazepine and its epoxide metabolite can be converted with triethylamine and tri- fluoroacetic acid into a cyanide derivative, which has better chromatographic properties than the parent amide.8 Benzodiazepines are often chromatographed as their benzophenones after acid hydroly~is,~ but the metabolites would often be hydrolysed to the same benzophenone as the parent drug, which makes this procedure of little value in metabolic work.Selective detectors, such as the alkali flame-ionisation and electron-capture detectors, can improve the sensitivity of detection by as much as lo3 compared with flame-ionisation detectors.Infrared spectrophotometers can now be obtained that will produce spectra from 1-lOpg of material on-line to a gas chromatograph. However, for the separation and identification of drugs and their metabolites, combined gas chromatography - mass spectro- metry is probably the best technique; when used in the multiple-ion detection mode, this combination provides a very sensitive and specific method for quantitative work.2. 3. 4. 5. 6. 7. 8. 9. References Beckett, A. H., in Porter, R., and O’Connor, M., Editovs, “The Poisoned Patient: The Role of the Jonkman, J . H. G., Wijsbeek, J., Brouwer-de Boer, S.H., de Zeeuw, R. A., Van Bork, L. E., and McReynolds, W. O., J . Chvomat. Sci., 1970, 8, 685. Drozd, J., J . Chvomat., 1975, 113, 303. Ahuja, S., J. Phavm. Sci., 1976, 65, 163. Hartvig, P., Strandberg, S., and Naslund, B., J . Chvomat., 1976, 118, 65. Hucker, H. B., and Miller, J. K., J . Chromat., 1968, 32, 408. Gkrardin, A., Abadie, F., and Laffont, J., J .Phavm. Sci., 1975, 64, 1940. Hailey, D. M., J . Chromat., 1974, 98, 527. Laboratory,” Ciba Foundation, London, 1968, p. 57. Orie, N. G. M., J . Phavm. Phavmac., 1975, 27, 849. Application of H ig h - perf ormance Liquid Chromatography to Drug Metabolism G. G. Skellern Drug Metabolism. Research Unit, Department of Pharmaceutical Chemistry, University of Strathclyde, Glasgow, G1 1XW Various techniques have been used for the quantification of small amounts of drugs and metabolites in biological fluids.Included in these procedures are spectrophotofluorimetry, gas - liquid chromatography, thin-layer chromatography and radiochemical tracer techniques. High-performance liquid chromatography (HPLC) combines the advantages of other methods in providing adequate separation of compounds at room temperature with rapid quanti- fication of drug and metabolites.Operation at room temperature is advantageous when handling thermally labile compounds. HPLC has its widest application in the measurement of polar drugs and metabolites of high relative molecular mass that are difficult to assay by other procedures. The instrumentation and theoretical aspects of HPLC will not be discussed at length, as there are many published works on the ~ubject.l-~ The metabolism of a drug can occur in two phases.4 The phase 1 reactions involve oxi- dations, reductions and hydrolyses, while the phase 2 reactions are syntheses, commonly called conjugations.During a phase 1 reaction, an OH, NH, and CO,H group may be intro- duced or unmasked in the drug.These functional groups are then capable of undergoing reactions (phase 2) with activated substrates of glucuronic acid and sulphate, or being acti- vated themselves to react with endogenous compounds such as glycine, resulting in polar metabolites. The metabolites obtained after a phase 1 reaction may possess similar properties to those of the parent drug, which is usually lipid soluble, and therefore the procedural difficulties may358 ANALYTICAL CHEMISTRY OF DRUG METABOLITES Proc.Analyt. Div. Chem. SOC. not be as great in measuring phase 1 metabolites as for phase 2 metabolites. It is in the measurement and quantification of conjugates that HPLC could be used to advantage. There is a paucity of work in this area, although the glucuronide and sulphate conjugates of $-hydroxyacetanilide (paracetamol) have been measured and quantified in ultrafiltrates of human urine by using a pellicular anion-exchange column with gradient elution.5 The high relative molecular mass antibiotic adriamycin, used in the treatment of cancer, has been resolved from its metabolites by using a reversed-phase system (phenyl/Corasil) and gradient elution.Quantification was achieved in human plasma and urine by radioimmuno- assay.6 In collaboration with thyroid clinics in Glasgow, we have been studying the metabolism of the thiocarbamide antithyroid drugs. By using HPLC, methimazole, the active metabolite of carbimazole, could be detected in the plasma of patients receiving a single oral dose of carbima~ole,~ using a reversed-phase system (OPN/Porasil) .This original method was time consuming and lacked sensitivity but by using microparticulate material (10-pm alumina or silica) an on-column detection limit of 0.6 ng has been achieved.8 In further experiments using the developed HPLC systems, appreciable amounts of a metabolite, 3-methyl-2-thio- hydantoin, have been detected in the plasma, thyroid tissue and urine of patients receiving methimazole. It is now possible, by using a single extraction procedure and incorporating an internal standard, benzamide, to determine the methimazole and metabolite levels in biological material (Fig.1). HPLC was used as the final Durification steD for the isolation of the metabolite, after conventional column chromatogiaph y and prlparative thin-layer chromatography .1 U - L 0 2 4 6 8 Time/min Fig. 1. Chromatograms of plasma samples from a thyrotoxic patient receiving methimazole (10 mg) intravenously : (a) Control extract; and (b) test extract. Col- umn ( 1 0 ~ 0 . 4 6 cm) dry packed with Spherisorb alumina, 10 pm. Mobile phase, 2% V / V methanol in chloroform: flow velocity, 0.17 cm s-l ; detection, ultraviolet photometer, 254 nm.Peaks: 1, methimazole; and 3, benzamide (internal standard). 3-methyl-2-thiohydantoin ; 2, A 1,4-benzodiazepine, chlordiazepoxide (Librium), is known to be metabolised in man to give two major metabolites, desmethylchlordiazepoxide and the lactam, demoxepam. A specific HPLC method has been developed using a reversed-phase system (C,,/Corasil) for the identification and quantification of drug and metabolites in the plasma and urine from chronic alcoholics being treated with high doses of chlordia~epoxide.~ It was noticed that, in extractsDecembev, 1976 RESEARCH AND DEVELOPMENT TOPICS 359 obtained from plasma after day 3, another peak appeared on the chromatogram as a shoulder on the chlordiazepoxide peak, and, by altering the conditions, it was possible partially to resolve this metabolite.By use of adsorption chromatography (silica, 37-52 pm) it was possible to confirm that this new metabolite was N-desmethyldiazepam. The anti-inflammatory drug indomethacin (Indocid) is usually assayed by spectrophoto- fluorimetry. It is known that aspirin and frusemide, which are given concomitantly with indomethacin, interfere in the procedure and it is possible that its metabolites may also do so. By using a reversed-phase system (C,,/Corasil) it is possible to measure indomethacin in the presence of metabolites and these drugs without interference.1° I have tried to demonstrate that because of its versatility HPLC finds its application in drug metabolism in all its various forms as an analytical technique and an aid to the iso- lation and identification of drugs and metabolites in biological fluid. References 1. 2. 3. 4. .5. 6. 7 . S. 9. 10. Kirkland, J . J., “Modern Practice of Liquid Chromatography,” Wiley-Interscience, New York, Done, J . N., Knox, J . J . , and Loheac, J., “Applications of High-speed Liquid Chromatography,” Rajcsanyi, P. M., and Rajcsanyi, E. M., “High-speed Liquid Chromatography,” Marcel Dekker, Parke, D. V., Chemy Ind., 1976, 9, 380. .lnders, M. W., and Latoire, J. P., J . Chromat., 1971, 55, 409. Langore, J. J., Van Vunakis, H., and Bachur, N. R., Cancer Res., 1974, 34, 2546. Skellern, G. G., Stenlake, J . B., Williams, W. D., and McLarty, D. G., BY. J . Clin. Pharmac., 1974, Skellern, G. G., Knight, B. I., and Stenlake, J. B., J . Chromat., 1976, in the press. Skellern, G. G., Meier, J., and Whiting, B., paper presented a t the 8th International Conference on Skellern, G. G., and Salole, E. G., J . Chvovnat., 1975, 114, 483. 1971. Wiley-Interscience, London, 1974. New York, 1975. 1, 265. Chromatography and Electrophoresis, Brussels, 1975.

ISSN:0306-1396    

DOI:10.1039/AD9761300352

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

Decembev, 1976 RESEARCH AND DEVELOPMENT TOPICS 359 Research and Development Topics in Analytical Chemistry The following is a summary of one of the papers presented at the Analytical Division Meeting on Research and Development Topics in Analytical Chemistry held on May 4th and 5th, 1976, at the University of Exeter. Summaries of seven other papers presented at the Meeting appeared in the November issue of Proceedings (p.326). The Enthalpimetric Determination of Some Constituents of Dolomite M. A. H. Al-Gifri and L. S. Bark Ramuge Labovatovies, Univevsity of Salfovd, Salfovd, M5 4 WT Dolomite is widely used industrially and while for some purposes a knowledge of the pro- portion of major components only is required, for many procedures it is necessary that a more detailed assay is readily available.The percentage composition by mass of a typical sample of dolomite is: CaO = 31 ; MgO = 20; CO,(H,O) = 47; SiO, = 1 ; Fe203 = 0.25; A1203 = 0.15; MnO = 0.05. (Components present at a level of less than 0.01% are Na,O, K20, L1,0, Cr2O3 and TiO,). The present work is restricted to an assay of those components that are present in amounts greater than 0.1% m/m. In order to obtain a rapid procedure capable of being used for routine purposes, it is essential that there can be sequential analysis of several constituents in the same sample and that separation of the various constituents into workable groups is rapid and easy.The advan- tages of using direct-injection enthalpimetry for the assay of some minerals have already been reviewedl and, from a consideration of these advantages and of some of the major work in this particular field,2 it was thought that direct-injection enthalpimetry would be a suitable tech- nique and that the procedures previously published for the determination of one or two con-360 RESEARCH AND DEVELOPMENT TOPICS Proc. AnaZyt.Div. Chem. SOC. stituents could be modified and extended to include several constituents.One essential factor in all sequential titration schemes, and especially when using a comparative technique such as direct-injection enthalpimetry, is that- the progress of the analyte assays must reflect the conditions used in the preparation of the calibration graphs. Thus, if the calibration graphs for the analytes are determined using a particular sequence of addition of reagents and fixed amounts of the selected reagents over restricted ranges of concentration of the analytes, then the same procedure must be employed in the assay.The heat capacities of the system, at certain points in the assay, must lie within narrow confines in order to ensure that a linear relationship obtains between the heat evolved per millimole of the analyte then reacting and the temperature changes in the relevant system.The sensitivity of the system was varied by suitable shunting of a potentiometric recorder having a normal sensitivity of 1 mV for a full-scale deflection, i.e., 1 mV f.s.d., and it was generally adjusted in steps SO that the signal received in each injection sequence was at least 100 mm and consequently the error arising from any reading should not have been more than 0.5%.The chemical procedure consists of the dissolution of the powdered sample in hydrochloric acid, separation of the silica as hydrated silica and then separation of the filtrate into two portions : a portion containing those metals whose hydroxides are precipitated from an ammonia - ammonium chloride medium (pH lo), vix., manganese( 11), iron(I1) and aluminium- (111) ; andaportion containing those metals that have soluble, stable ammines, vix., manganese- (If), calcium(I1) and magnesium(I1).In each group the manganese(I1) is determined first, using a medium of pH 7 and oxidising the manganese(I1) to manganese(1V) with permangan- ate. In the ammine group, the calcium is then determined by precipitation of the oxalate, the heat of the precipitation reaction being sufficient to give a suitable heat pulse in the system used.After adjustment of the pH, magnesium is then precipitated as the ammonium magnesium phosphate. Thus the 15 ml of sample is treated sequentially with 1 ml of pH 7 buffer and then 1 ml of saturated potassium permanganate solution.One millilitre of 3 M ammonium oxalate is then injected, 3 drops (about 0.2 ml) of 4 M sodium hydroxide solution are added and then 1 ml of 2 M sodium phosphate solution is injected. (One can thus see the need for having a standard sequence as the phosphate addition is to a volume of 18 ml, already containing excess amounts of previously added reagents.) In the hydroxide groups, after oxidation of the manganese(II), the iron(II1) and excess of permanganate are reduced with ascorbic acid before precipitating the aluminium as sodium dipotassium hexafluoroaluminate- (111).The heat of this redox reaction is high and the sensitivity of the recorder needs to be decreased. The enthalpimetric apparatus used has been previously de~cribed.~ The iron(I1) is then re-oxidised to iron(II1) using persulphate.The results of the assay of dolomite are given in Table I. Analytc Silica Mn(I1) A1 (I I I) TABLE I SOME TYPICAL ASSAYS OF DOLOMITE Reaction used H2SiF, --f K2SiF, Mn(I1) --f Mn(IV) Al(II1) -t Na+ + Kf +- F- --f NaK,[AlF,] Ca2f --f Ca oxalate Mg2+ -+ MgNW,PO, Fe(I1) --f Fe(ZI1) (PPt.) (PPt.) (PPt.) (PPt.1 Rangel r n M x 10-2 10-50 25-220 16-50 5-1 10 50-400 20-220 5-25 References Sensitivity for f.s.d./mV 2 5 1 5 5 5 10 Coefficient of variation, yo 0.30 0.34 0.32 0.50 0.30 0.16 0.30 1. 2. 3. Bark, L. S., and Bark, S. M., “Thermometric Titrimetry,” Pergamon Press, Oxford, 1968. Sajo, I., and Sipos, B., Radex Rdsch., 1968, 178. Bark, L. S., and Grime, J. K., Analyst, 1972, 97, 911.

ISSN:0306-1396    

DOI:10.1039/AD9761300359

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

December, 1976 EQUIPMENT NEWS 361 Equipment News Differential Scanning Calorimeter The Setaram differential scanning calorimeter is a quantitative differential thermal analyser that can also measure specific heats. The heart of the calorimeter is a programmable reference block contained in an enclosure whose exterior is at ambient temperature. Two refractory tubes traverse the middle of the enclosure and the block, the mid-section forming the sample holder and detector. A heat-flow calorimetric detector, formed from thermocouples thermally connected to the reference block utilising the Tian-Calvet method, covers the middle zone.A gas-circulation system is incorporated for rapid cooling of the calorimetric block and an auxiliary liquid-nitrogen system is added for sub-ambient work.A digital electronic programmable con- troller uses the most modern temperature- control techniques, and samples with or without a container can be examined, including those from an evolved gas analyser. TEM Sales Ltd., Gatwick Road, Crawley, Sussex. Infrared Analysis The Wilks Model 80 is a new, compact micro- computer-controlled infrared spectrometer. It accommodates a wide variety of sample- handling accessories, controls all instrument settings and obtains quantitative data on solids, liquids and gases.A simplified 16-key system for entry of instrument settings and factors for data manipulation is featured and up to 5 individual analyses can be pre-programmed and retrieved by simple key-board selection. High accuracy is claimed because of the high signal- to-noise ratio and, through signal averaging, 256 measurements are made at each wavelength over a 1/180-s interval.Up to 17 separate wavelengths can be measured in less than 2 min and the interval between sets of measurements is variable from 7 s to 30 min. The computation matrix for each analysis can be programmed into the microcomputer for the rapid production of concentration information. A digital print- out of results is provided and computer interface with an RS 232C format communication link is available.Wilks Scientific Corporation, P.O. Box 449, S. Norwalk, Connecticut 06856, USA. Air-monitoring Equipment A range of five new products for air-pollution monitoring is announced. The range includes a bacteriological detector that is used to determine the number of airborne particles containing viable organisms, and a sensitive digital dust indicator, which is said to measure accurately the concentration of airborne dust in the size range 0.001-100mgm-~.The re- maining products are an indicator for measuring smoke densities from ducting and chimneys, a mains-powered dust sampler and a pocket-sized personal sampler.The last mentioned has a size-selective cyclone unit attached for separat- ing respirable from non-respirable dust. Rotheroe & Mitchell Ltd., Unison Public Relations Ltd., 13/17 Southgate Road, Potters Bar, Herts., EN6 5DS. Clean-up Kits Another in the series of Baker safety clean-up kits has recently been released. It is intended to deal with spillages of up to 0.5 1 of con- centrated solutions of sodium, potassium or ammonium hydroxide.Neutracit (TM) comes as a powder and is applied from the perimeter inwards with thorough mixing. A colour indicator is incorporated in order to indicate neutrality and the mixture is taken up in Liquisorb prior to disposal. Also supplied are safety glasses and gloves, scoops and full instructions. Other kits are available, including one for mercury spillages. Linton Instrumentation, Hysol, Harlow, Essex, CM18 6QZ.Sterile Work Cabinets The Hepaire vertical and horizontal laminar- flow modules are now manufactured in a wider range of sizes but the laminar mode 100 &- 10 f.p.m. is unchanged. As an alternative to high-density chipboard bonded to white mela- mine laminate there is now a choice of stove- enamelled mild steel or stainless steel with Hepaire acoustic insulation.In addition to the free-standing units, modules ready to be suspended for vertical laminar-flow applications or to be mounted on legs for mobile clean rooms, etc., are now available. The same company constructs various custom-built extract fume hoods and cupboards in a range of materials.Hepaire Manufacturing Ltd., Water Lane, Storrington, Sussex, RH20 3DN. General-purpose Titrator The Ionics Digichem general-purpose titrator will measure inorganic and organic titratable species in both aqueous and non-aqueous media. Unlike conventional titrators the Digichem is capable of measuring two end-points during362 EQUIPMENT NEWS Proc. Analyt. Div. Chem. SOC. each cycle.These end-points are determined by measuring the first derivative of the potentio- metric titration curve, thus giving high accuracy without the need for electrode calibration. Applications include pH control and EDTA titrations for measurements such as carbonates and hydroxides in gas scrubbers, weak and strong acid mixtures and mercury in caustic soda. Techmation Ltd., 58 Edgware Way, Edgware, Middx., HAS SJP.Multi-channel Pipettes Jencons (Scientific) Limited, the distributor in the UK for Fix-Finn micropipettes, announce two new models. These models are multi- channel with four or eight polypropylene tips and are designed for liquid dispensing and serial dilution work. Each multi-channel model delivers a fixed volume from each of its four or eight heads and is available in 22 unit sizes from 5 to 200 pl.Multiple dispensing work can be carried out four or eight times quicker than with a single-headed type, resulting in considerable savings in work and time. Jencons (Scientific) Ltd., Mark Road, Heme1 Hempstead, Herts. Leak Detectors The new 936 Series Helium Mass Spectrometer Leak Detectors is announced. High-production leak testing is offered with increased reliability and low maintenance.The automated trapless model, the 936-70, eliminates the need for a liquid-nitrogen cryogenic trap and is claimed to be faster, more convenient and more economical than previous detectors. There are two other models in the series: the 936-60, a versatile standard leak detector, and the 936-65, an ultra-sensitive model with fast helium clean-up for high-sensitivity applications.Varian Vacuum Division, 12 1 Hartwell Avenue, Lexington, Ma. 02173, USA. Distillation and Extraction Equipment A wide range of distillation and extraction equipment is now available with associated electronics enabling custom-built apparatus to be supplied for specific requirements. The system is essentially modular in respect of glassware and electronic relays, timers, tem- perature indicators, power supplies, etc., which enables requirements to be met more quickly.Orme Scientific Ltd., P.O. Box 3, Stakehill Industrial Estate, Middleton, Manchester, M24 3KH. Digital Humidity and Temperature Indicator The Digital-Humitemp utilises the well-proven PCRC-11T humidity sensor in conjunction with two precision G-3 1 platinum glass-sealed tem- perature sensors.One of the temperature sensors is used for the direct temperature read- out while the other compensates the temperature coefficient of the humidity sensor. All three sensors are housed in a compact, protected assembly and transistorised circuitry is used with 3-digit type panel meters. The read-outs for both humidity and temperature are linearised and cover the ranges O-lOO% relative humidity and 0-100 "C.Automatic temperature com- pensation for the humidity sensor is operative from -5 to +75 "C. Provision is made for connection to recorders, computers, etc. Linear analogue output signals for both humidity and temperature are available. International Instruments Ltd., Cross Lances Road, Hounslow, Middx.Ultraviolet Detector The Model 226 is a low-cost, high-performance, dual-beam, liquid-chromatographic monitor operating at 254 and 280 nm. It has the high sensitivity and stability required for high- performance liquid chromatography and the wide absorbance ranges suitable for conventional columns. MSE Scientific Instruments, Manor Royal, Crawley, Sussex. Gas Chromatography A new dual nitrogen - phosphorus sensitised detector is announced.The dual base is identical with that in Hewlett Packard's flame- ionisation detectors but three pairs of collector assemblies are provided. They allow each half of the detector to be used as a normal flame- ionisation detector, as a self-igniting flame detector when very large peaks may cause flame blow-out, or as a nitrogen - phosphorus detector.Change-over is said to be rapid and the collectors can be used in any combination. The detector works equally well with nitrogen or helium carrier and the control box houses power supplies for heating the alkali salt activator and regulators and gauges to control hydrogen and air flows. Hewlett Packard Ltd., King Street Lane, Winnersh, Wokingham, Berks., RG11 5AR.New Literature Isoklene is a solvent filtered down to 0.2 ,urn that has been developed for cleaning electronicDecember, 1976 ANALYTICAL CHEMISTRY TRUST FUND 363 components, delicate precision instruments, etc. A new data sheet is available on request. Micro-Image Technology Ltd., Greenhill Industrial Estate, Riddings, Derby, DE5 4UB. A new concise catalogue is available that des- cribes and illustrates the full range of instrumen- tation, tape recorders/reproducers, direct writ- ing/recording systems and signal conditioning.Bell & Howell Ltd. , Electronics & Instruments Division, Lennox Road, Basingstoke, Hants., RG22 4AW. A brochure published by Infotronics Limited describes their Model CRS 304 integrator.In- cluded is an illustration of four separate, consecutive print-outs from an analyser of a mixture of cyclohexanol and cyclohexanone, together with four print-outs from an analysis of a light-petroleum distillate on a glass capil- lary column. Irish Export Board, Ireland House, 150 New Bond Street, London, W1Y OHD. Gas mixtures for calibration and instrumentation are described in an eight-page brochure in which reference is made to three types of gas mixture, viz., gravimetric, certified and unanalysed. Air Products Ltd., Special Products Depart- ment, Weston Road, Crewe, Cheshire. A product summary catalogue of particle size analysis and random sampling instruments is available from Microscal. Microscal Ltd., 20 Mattock Lane, Ealing, London, W5 5BH. A catalogue containing hints for the user and details of portable thermoregulators, circulators, thermostatic water-baths, coolers and dri-block heaters is available on request from Techne (Cambridge) Ltd., Duxford, Cambridge, CB2 4PZ.Data sheets and information on the Junkalor (East German) series of gas analysers and calorimeters are now available from their UK representatives. Kandem Electrical Ltd., 7 11 and 7 15 Fulham Road, London, SW6 5UN.Brandenburg Ltd., Nuclear Engineering Division, 939 London Road, Thornton Heath, Surrey, CR4 6JE. A comprehensive brochure, which is available on request, describes the cryogenic and magnet systems available and provides substantial technical detail. Oxford Instruments, Osney Mead, Oxford, OX2 ODX. A catalogue covering their range of air pollution monitors is available free from Techmation. Included are portable and laboratory - field models for rapid real-time analysis of ambient concentrations of suphur compounds, oxides of nitrogen, ozone and hydrocarbons, plus over 300 toxic gases and vapours, to below TLV levels. Flue-gas monitoring equipment is also described. Techmation Ltd., 58 Edgware Way, Edgware, Middx., HA8 8JP. A shortform catalogue on the 4000 series multi- channel analysers in announced. These analysers are based on the mechanical rack system originally developed by the UKAEA, Harwell.

ISSN:0306-1396    

DOI:10.1039/AD9761300361

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

December, 1976 ANALYTICAL CHEMISTRY TRUST FUND Ana I yti ca I 363 Chemistry Trust Fund SAC Fellowships The Trustees invite proposals for research projects likely to make major contributions to the advancement of analytical chemistry in the UK. Proposals will be considered from qualified applicants in non-academic establish- ments such as industrial organisations, govern- ment laboratories and Research Associations, as well as from those in academic institutions. Applications must be made by prospective Fellows only.The value of a Fellowship is related to the Lecturer scale for non-clinical academic staff ( i 3 400 per annum minimum, plus a London allowance of f1450 where appli- cable). SAC Studentships The Trustees invite proposals from supervisors for research projects likely to make important contributions to the advancement of analytical chemistry in the UK and which are suitable for well qualified postgraduate students. Applica- tions may be submitted by research supervisors who must be members of the Analytical Division of The Chemical Society of a t least 2 years’ standing. Proposals for projects to start in the autumn term of 1977 will be considered early in that year when a tentative award may be364 CONFERENCES made, subject to the Trustees being satisfied by the summer of 1977 that a student acceptable to them is available.The value of a Studentship is between ,5925 and ~l380perannumminimum, according to circumstances, plus fees. Application Regulations for the Fellowships and the Studentships can be obtained from the Secre- tary, Analytical Division, The Chemical Society, Burlington House, London, W1V OBN. The closing date for applications is February 28th, 1977. AND MEETINGS Proc. Analyt. Div. Claem. SOC. __

ISSN:0306-1396    

DOI:10.1039/AD9761300363

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

364 CONFERENCES AND MEETINGS Proc. Analyt. Div. Chem. soc. Specialised Course on Scanning Electron Microscopy for Biologists and Materials Scientists. Further details can be obtained from: The Administrator, Royal Microscopical Society, 37/38 St. Clements, Oxford, OX4 1AJ. Conferences and Meetings Royal Microscopical Society 1977 The Programme of Meetings and Courses of The Royal Microscopical Society for 1977 in- cludes the following : January 11, Guy’s Hos#ital, Lopzdon : Annual Histochemistry Meeting.March 28-APril 1, University of Leeds: Course on Principles of Electron Microscopy. March 28-30, University of Leeds : Specialised Course in Transmission Electron Micro- scopy. March 30, University of Leeds: First Annual EM Meeting. March 31-April 1, Univevsity of Leeds: Microscopical and Allied Structural Studies of Polymers and Fibres.April 3-7, University of Cambridge : First International Low Temperature and Analysis Meeting. July 4-8, Brunel University, Uxbvidge : Course on Principles of Light Microscopy. Jzdy 11-1 5, Brunel University, Uxbridge : Course on Photomicrography. July 11-15, Brunel Univevsity, Uxbridge : Course on Microscopy of Materials. July 25-29, Univevsity of Technology, Laugh- borough : Polarised Light Microscopy Course.September 5-9, University of Oxford : Course on Specialised Techniques in Fluorescence Microscopy. September 12-16, Univevsity of Edinbuvgh : Principles of Light Microscopy. September 13-15, University of Edinburgh : Microscopy of Macromolecules. Septembev 26-30, University of Cambridge : 9th National Atomic and Molecular Physics Conference April 4-7, 1977, Reading University The Conference is not intended to be highly specialised and should be of particular interest to research students.Further details, registration forms and instructions on the preparation of abstracts of contributed papers are available from K. Codling, Conference Secretary, J .J. Thomson Physical Laboratory, Whiteknights, Reading, RG6 2AF. EMAG ’77. Developments in Electron Microscopy and Analysis September 12-14, 1977, Glasgow The Electron Microscopy and Analysis Group of The Institute of Physics is arranging a three- day conference on scanning and transmission electron microscopy and analysis, to be held at the University of Glasgow. Topics covered will include instrumentation, image detection and processing, microanalytical techniques and methods, specimen manipulation, electron optics and beam - specimen interaction.A call for papers will be made in March 1977. A trade exhibition of instruments, equipment and accessories will run concurrently with the conference. Further information will be available from the Meetings Officer, The Institute of Physics, 47 Belgrave Square, London, S W l X SQX.International Bioanalytical Forum on the Assay of Biological Samples for Drugs and Other Trace Compounds September 12-15, 1977, Guildford The programme for this Forum will include a manufacturers’ exhibition and “poster presenta- tions” on the following subjects: “The Scope of HPLC” ; “The Effectiveness of Different Ana- lytical ApproachesJJ ; “Analytical Case Histories -the Rationale of Method Development” ; “Gas-chromatographic Technology for Sub- nanogram Loads” ; and “Mass Spectrometry as an Assay Tool.” Further information can be obtained from Dr.E. Reid, University of Surrey Wolfson Bioanalytical Centre, Guildford, Surrey, GU2 5XH.December, 1976 PUBLICATIONS RECEIVED Particle Size Analysis Conference Septembev 13-15, 1977, Salfovd This Conference is being organised by the Particle Size Analysis Group of the CS Analytical Division and is to be held at the University of Salford.It is envisaged that all aspects of particle characterisation will be covered, including measurement of particle-size distribution and surface area ; measurement of single-particle characteristics such as shape and pore-size distribution ; associated ancilliary techniques, such as sampling, dispersion and particle- density measurement ; and the application of particle-characterisation methods in applied sciences concerned with pharmaceuticals, cera- mics, powder metallurgy, etc.The following Plenary Lectures will be given : “Particle Characterisation-A Current Assess- ment,” by Professor Clyde Orr (Georgia Institute of Technology) ; “Sieving-A Review,” by Professor Dr. Ing Kurt Leschonski (Technische Universitat Clausthal) ; and “Particle Size Measurement in the Sub Micron Region,” by W. Carr [Ciba-Geigy (UK) Ltd.]. Contributed papers are invited and abstracts should be submitted by December 31, 1976. Further details can be obtained from the Honorary Secretary to the Local Organising Committee for the Particle Size Analysis 1977 Conference: Dr. D. Dollimore, Reader in Physical Chemistry, University of Salford, Salford, M5 4WT. 365

ISSN:0306-1396    

DOI:10.1039/AD9761300364

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

December, 1976 PUBLICATIONS RECEIVED 365 Theory and Applications of Molecular Diamagnetism. Edited by L. N. Mulay and E. A. Boudreaux. Pp. xiv + 321. New York, London, Sydney and Toronto: John Wiley & Sons. 1976. Price f122.50; $39. Publications Received Recycling Waste. Paul I . Slee Smith. Pp. xvi + 175. Broxley, Shropshire : Scientific Publications (G.B.) Ltd. 1976. Tabellen zur Strukturaufklarung organi- scher Verbindungen mit spektroskopischen Methoden. E.Pretsch, T. Clerc, J. Seibl and W. Simon. Anleituvzgen fiiv die chemische Labovatovium- spyaxis, Band XV. Pp. x + 307. Berlin, Heidelberg and New York : Springer-Verlag. 1976. Quadrupole Mass Spectrometry and its Applications. Edited by Peter H. Dawson. Pp. xxii + 349. Amsterdam, Oxford and New York: Elsevier Scientific Publishing Company.1976. Price Dfl129; $49.75. Annual Reports on Analytical Atomic Spectroscopy, Reviewing 1975. Volume 5. Edited by C. W. Fuller. Pp. viii + 267. London : The Chemical Society. 1976. Price Ll5. CRC Handbook of Chemistry and Physics. 57th Edition. 1976-1977. Edited by Robert C. Weast. Pp. xii f 2393. Cleveland, Ohio: CRC Press, Inc. 1976. Price $29.95.Identification & Analysis of Organic Pollutants in Water. Edited by Lawrence H. Keith. Pp. x + 718. Ann Arbor, Michigan: Ann Arbor Science Publishers Inc. 1976. Price L17.90; $30.25. Solutions and Solubilities. Part 11. Edited by Michael R. J. Dack. Techniques of Chemistvy, Volume VIII. Pp. xii + 499. New York, London, Sydney and Toronto: John Wiley & Sons, Inc. 1976.Price i24.50; $44.60. NMR. Basic Principles and Progress. Volume 13. Introductory Essays. Edited by M. N. Pintar. Lectures fvovn the Intevnational Summev School on Nucleav Magnetic Resoname, Univevsity of Watevloo, June 23-28, 1975. Pp. xii + 154. Berlin, Heidelberg and New York: Springer-Verlag. 1976. Price DM72; $29.60. Struktur und Absorptionsspektroskopie organischer Naturstoffe.Manfred Kraft. Wissenschaftliche Fovschungs- bevichte. Reihe 1 : Gvundlagenfovschung und gvundlegende Methodik Abteilung A : Chemie und Physik. Band 76. Pp. xii + 321. Darmstadt: Dr. Dietrich Steinkopff Verlag. 1976. Price DM98. Analysis Instrumentation. Volume 14. Edited by J. F. Combs, R. W. Sims and F. Martin. Pvoceedings of the 22nd Annual ISA Analysis Instvumentation Symposium, M a y 9-12, 1976, S a n Fvancisco, Califovnia.Pp. viii + 125. Pittsburgh, Pennsylvania: Instru- ment Society of America. 1976. Price i9.76; $16.50.366 PUBLICATIONS RECEIVED Proc. Analyt. Div. Chern. SOC. Microscale Manipulations in Chemistry. T. S. Ma and V. Horak. Chemical Analysis, Volume 44. Pp. xvi + 488. New York, London, Sydney and Toronto: John Wiley & Sons, Inc.1976. Price L19.40; $33.00. Analysis of Essential Oils by Gas Chrom- atography and Mass Spectrometry. Yoshiro Nasada. Pp. xiv + 334. New York London, Sydney and Toronto : Halsted Press. 1976. Price k28.90; $49.70. Chromatography of Steroids. Erich Heftmann. Jouvnal of Chromatogvaphy Libvavy, Volume 8. Pp. xiv + 203. Amster- dam, Oxford and New York. Elsevier Scientific Publishing Company.1976. Price Dfl90; $34.75. Isotachophoresis. Theory, Instrumentation and Application. Frans M. Everaerts, Jo L. Beckers and The0 P. E. M. Verheggen. Jouvnal of Clzuomato- gvaphy Libvavy, Volume 6. Pp. xiv + 418. Amsterdam, Oxford and New York: Elsevier Scientific Publishing Company. 1976. Price Dfl160; $61.50. The Quality Control of Medicines. Edited by P. B.Deasy and R. F. Timoney. Pvoceedings of the 35th Intevnational Congress of Phavmaceutical Sciences, Dublin 1975. Pp. xiv + 398. Amsterdam, New York and Oxford : Elsevier Scientific Publishing Com- pany. 1976. Price Dfl100; $38.50. Selected Annual Reviews of the Analytical Sciences Volume 4 Edited by Dr L. S. Bark, University of Salford The fourth volume continues the policy adopted in previous volumes of presenting critical reviews of selected topics in modern analytical science.Each of these reviews embodies the work considered pertinent over the four or five years up to 1974. 'Advances in Voltammetric Techniques,' by B. Fleet and R. D. Jee: Advances in Instrumentation and Recent Applications of Voltammetric Techniques in the Areas of DC Polarography, Pulse Polarography, AC Polarography, Stripping Voltammetry. 'High- frequency Electrodeless Plasma Spectrometry,' by B. L. Sharp: Classification of Plasma Types; Emission Spectrometry- General Considerations; Nebulisers; The Inductively-coupled Radio-frequency Plasma Torch; The Microwave Plasma. 73 pages Price f 9.50 ISBN 0 85990 204 8 Members of The Chemical Society may buy personal copies at the special price of f3.00 provided they order direct and enclose remittance. Obtainable from the Publications Sales Officer, The Chemical Society, Blackhorse Road, Letchworth, Herts., SG6 1 HN

ISSN:0306-1396    

DOI:10.1039/AD9761300365

出版商:RSC    

年代:1976

数据来源: RSC

摘要:

Zleceutzbev, 1976 REPRINTS OF REVIEW PAPERS 367 Reprints of Review Papers Reprints of the following Review Papers published in The Analyst since 1967 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 jS1; orders for six or more reprints of the same or different Reviews are subject to a discount of 25%.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, 1967). “Precipitation from Homogeneous Solution,” by P. F. 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 Steel,” by P. H. Scholes (April, 1968). “Inorganic Ion Exchange in Organic and Aqueous - Organic Solvents,” by G. J. Moody and J. D. R. Thomas (September, 1968). “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 Kl&ra 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, K. T6th 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). “Chemiluminescence 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). “Properties and Uses of the Colorimetric Reagents 2-Nitroso-5-dimethylaminophenol and 2-Nitroso-5-diethylaminophenol for Cobalt,” by Kyoji ‘TOei and Shoji Motomizu (July, 1976). and E. A. Walker (February, 1967). (April, 1967). 11. Egan (August, 1967). McMillan (September, 1967). D. W. Wilson (November, 1967). Part 11. Part 111. Stagg (January, 197 1). Spectroscopy,” by G. F. Kirkbright (September, 1971). (October, 1971). by J . M. Clifford and W. Franklin Smyth (May, 1974). “Fibre Tdcntification and Analysis of Fibre Blends,” by H. M. Appleyard (August, 1976).

ISSN:0306-1396    

DOI:10.1039/AD9761300367

出版商:RSC    

年代:1976

数据来源: RSC