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Proceedings of the Society for Analytical Chemistry,
Volume 1,
Issue 3,
1964,
Page 008-009
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1 . Proceedings of the Society for Proc. SOC. Anal. Chem. Vol. I No. 3 Pages 13-24 Analytical Chemistry CONTENTS Medal of the Society . . . . 13 Reports of Meetings Annual General Meeting . . 13 “The Assay of Penicillins” . . 15 Papers accepted for The Analyst 21 Publications Received . . . . 22 Notices . . .. . . . . 23 Forthcoming Meetings . . Back cover Section Meetings . . . 14 Membership changes . .. 22 March 1964 Vol. I No. 3 March 1964 PROCEEDINGS THE SOCIETY FOR ANALYTICAL CHEMISTRY OF President of the Society D. C. Garratt Hon. Secretary of the Society S. A. Price Hon. Treasurer of the Society D. T. Lewis C.B. Hon. Assistant Secretaries of the Society B. S. Cooper; D. W. Wilson Secretary Miss P. E. Hutchinson 14 BELGRAVE SQUARE LONDON S.W.1 Telephone BELgravia 3258 Editor J.B. A t t r i l l Proceedings is published by The Society for Analytical Chemistry and distributed t o members and all subscribers t o The Analyst without charge Single copies may be obtained direct from the Secretary The Society for Analytical Chemistry a t the above address (NOT through Trade Agents) price 2s. 6d. post free. Remittances payable t o “Society for Analytical Chemistry” MUST accompany orders Determination of Trace Elements with Special Reference to Fertilisers and Feeding Stuffs A Report of the Analytical Methods Committee Recommended methods for determining traces of- B Ca CI- Cr Co Cu F I Fe Mg Mn Mo Ni Se Zn Pp. viii + 39 21s. net Members of the Society for Analytical Chemistry are entitled t o buy copies at the special Members’ price of 12s. 6d. provided they order direct from Remittances made out t o “Society for Analytical Chemistry” must accompany Members’ orders The Editor The Analyst 14 Belgrave Square London S.W.1 Published for the Society for Analytical Chemistry W. HEFFER & SONS LTD. PETTY CURY CAMBRIDGE by
ISSN:0037-9697
DOI:10.1039/SA96401FX008
出版商:RSC
年代:1964
数据来源: RSC
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Back cover |
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Proceedings of the Society for Analytical Chemistry,
Volume 1,
Issue 3,
1964,
Page 010-011
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SAC CONFERENCE July 19th-23rd 1965 THE Society for Analytical Chemistry has in hand the preliminary arrangements for a Con- ference to be known as the SAC Conference in July 1965. Founded in 1874 and one of the oldest bodies in the world concerned with the subject the Society had as its primary objective-“to encourage assist and extend the knowledge and study of analytical chemistry.” It has continued to pursue these aims noticeably since 1945 a period in which the conception of what constitutes “analytical chemistry” and what an “analyst” has been extended. I t has played its part during these last two decades in a number of ways including the formation of specialist groups and discussion panels and the holding of symposia on specialist topics and of sectional conferences. The membership of the Society has not only grown during this period but has also been extended to include physicists biologists engineers and others concerned with the application of or who ha1.e contributed to the advancement of modern analytical techniques.In furtherance of its policy the Society will hold a Conference in 1965 at which an account of original investigations in any part of the wide field of modern analytical chemistry may be presented and discussed. I t has been decided to base the Conference at a Cniversity and Xottingham has been selected since it provides all the facilities which are considered necessary. The University is magnificently situated in its own parklands about 4 miles from the centre of the City. The scientific and social functions will be held in the University buildings and excellent living accommodation has been booked in modern Halls of Residence which provide the maximum of comfort.A full social programme including receptions excursions and a ladies’ programme will be arranged. The Conference fee will include registration pre-prints of papers a bound copy of the Proceedings local transport and all social functions (except the Banquet) ; it will be El0 lOs. or k15 15s. for a delegate accompanied by a lady guest. The cost of accommodation at Halls of Residence (Sunday p.m. to Saturday a.m.) will be about E l l inclusive of gratuities. Those who wish to offer a paper for consideration by the Executive Committee are asked to indicate their intention at the time they write for preliminary registration. Papers should describe original unpublished work that makes some positive contribution to the advance- ment of any sector of the broad field of analytical chemistry and should not be of a review nature.Those who wish to be kept informed of arrangements and to receive enrolment papers when available should write (in BLOCK letters please) name qualifications and full address and also the words “SAC Conference 1965,” on a postcard and send it to Mr. A. S. Beidas B.Sc. F.R.I.C. Standards Department Boots Pure Drug Co. Ltd. Station Street Notting- ham England preferably before March 31st 1964. Typescripts must not exceed 5000 words. SAC CONFERENCE 1965 If you have nDt yet applied W R I T E NO‘W I SOCIETY FOR ANALYTICAL CHEMISTRY Forthcoming Meetings March Friday 20th DUNDEE Tuesday 24th NOTTINGHAM Tuesday 24th LONDON April Thursday 2nd LONDON Wednesday 15th LONDON Friday 17th CARLISLE Wednesday 22nd LUTON Wednesday 29th LONDON SCOTTISH SECTION Ordinary Meeting.“Organic Analytical Reagents-A Survey of Some Recent Work,” by W. I. Stephen B.Sc. Ph.D. A.R.I.C. Queen’s College Dundee; 5.05 p.m. (Please note change of time.) MIDLANDS SECTION Ordinary Meeting. “The Work of the Public Analyst,” by R. -1. Dalley F.R.I.C. Nottingham and District Technical College Burton Street Nottingham PHYSICAL METHODS GROUP Ordinary Meeting on “Physical Methods Applied “Analytical Methods in Archaeology,” by -1. E. A. Werner M.A. M.Sc. 7 p.m. to the Examination of Archaeological Remains.’ ’ D.Phi1. “Spectrographic Methods in Xrchaeometry,” by E. T. Hall M.A. D.Phi1. Meeting Room of the Chemical Society Burlington House Piccadilly London W.1 ; 6.30 p.m. SOCIETY Ordinary Meeting for Contributions from Research Workers in “The Automation of Anion-exchange Chromatography of Phosphorus “Kinetic Studies in Bromate Titrimetry,” by J . M. Ottaway B.Sc. “Use of Liquid Anion Exchangers in Analytical Chemistry,” by A. I). “Some Applications of Thermogravimetric Xnalysis,” by A. W. Coats B.Sc. “The Spectrographic Determination of Beryllium in Fluorite Minerals ” by D. N. Waters M.A. D.Phi1. “The Gravimetric Determination of Iron by the Homogeneous Precipitation of Tris(2-thiopyridine-N-oxide) Iron’”,” by J. -4. \V. Dalziel Ph.D. D.I.C. A.R.C.S. F.R.I.C. and M. Thompson B.Sc. A.R,C.S. A.R.I.C. Universities and Colleges of Advanced Technology. Anions,” by G. Nickless Ph.I>. and D. Rogers B.Sc. Damodaran M.Sc.University College Gower Street London W.C. 1 ; 2.30 p.m. THIN-LAYER CHROMATOGRAPHY DISCUSSIOK PANEL One-day Meeting. papers will be presented and a brains-trust will be held. A manufacturers’ exhibition of apparatus and chemicals has been invited. Middlesex Hospital Medical School London W. 1 ; 10 a.m. NORTH OF ENGLAND SECTION and SCOTTISH SECTION Joint Meeting. “Fluorine and Teeth Decay,” by G. N. Jenkins M.Sc. Ph.D. “Chemical Additives in Foods,’’ by J. Markland B.Sc. F.R.I.C. Central Hotel Victoria Viaduct Carlisle ; 7.15 p.m. MIDLANDS SECTION Ordinary Meeting. “Analytical Chemistry Chemical Analysis and the Analyst,” by R. C. Room 223 Luton College of Technology Luton; 6.45 p.m. BIOLOGICAL METHODS GROUP Ordinary Meeting on “Immunological Assay Speakers Professor P. G. H. Gell B.X. M.B. R.Ch. and ,4. J. Fulthorpe Meeting Room of the Chemical Society Burlington House Piccadilly London Six Chirnside F.R.1 .C. of Hormones.” M.B. B.S. D.T.M. & H. W.l; 7 p.m. PRINTED BY W. HEFFER & SONS LTD.. CAMBRIDGE. ENGLAND.
ISSN:0037-9697
DOI:10.1039/SA96401BX010
出版商:RSC
年代:1964
数据来源: RSC
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Reports of meetings |
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Proceedings of the Society for Analytical Chemistry,
Volume 1,
Issue 3,
1964,
Page 13-14
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摘要:
March 1964 Reports of Meetings Vol. I No. 3 ANNUAL GENERAL MEETIKG THE ninetieth Annual General Meeting of the Society was held at 3 p.m. on Wednesday March 4th 1964 in the Meeting Room of the Royal Society Burlington House Piccadilly London W.1. The Chair was occupied by the President Dr. D. C. Garratt Hon. M.P.S. F.R.I.C. The Financial Statement for the year ending October 31st 1963 was presented by the Honorary Treasurer and approved and the Auditors for 1964 were appointed. The Report of the Council for the year ending March 1963 (to be published next month) was presented by the Honorary Secretary and adopted. The Scrutineers Miss A. Jones and Mr. P. W. Shallis reported that the following had been elected officers for the coming year- President-D. C. Garratt Ph.D. D.Sc. Hon.M.P.S. F.R.I.C.Past Presidents serving on the CounciZ-A. J. Amos K. C. Chirnside J. H. Hamence and Fice-Presidents-S. G. Burgess A. A. Smales and R. E. Stuckey. Hofzorary Treasurer-D. T. Lewis. Hoizorary Secretary-S. A. Price. Honorary Assistant Secretaries-B. S. Cooper (Programmes) and D. W. Wilson. Other 2Wernbers of Comcil-The Scrutineers further reported that 398 valid ballot papers had been received and that votes had been cast in the election of Ordinary Members of Council a.; follo\vs-- C. A . Johnson 291; G. W. C. Milner 277; E. Bishop 271; F. H. Pollard 261; H. J. Chiley 247; A. S. Beidas 211; G. Ingrarn 205; J. R. Edisbury 193; D. A. Pantony 148. The President declared the following to have been elected Ordinary Xembers of Council ,4. S. Reidas E. Bishop H. J. Cluley C. A. Johnson G.'Mi. C. Milner and F. H. Pollard. L. Brealey A. G. Jones E. Q. Laws I;. C. J. Poulton S. G. E. Stevens and C. Whalley having been elected members of the Council in 1963 will by the Society's Articles of Associa- tion remain members of the Council for 1964. 13 K . ,4. Williams. for the ensuing two years- 14 REPORTS OF MEETINGS [Proc. SOC. Anal. Chew. C. J. House (Chairman of the North of England Section) R. A. Chalmers (Chairman of the Scottish Section) E. A. Hontoir (Chairman of the Western Section) W. H. Stephenson (Chairman of the Midlands Section) D. W. Wilson (Chairman of the Microchemistry Group) L. Brealey (Chairman of the Physical Methods Group) and W. A. Broom (Chairman of the Biological Methods Group) will be ex-oficio members of the Council for 1964. NORTH OF ENGLAND SECTION A JOINT Meeting of the North of England Section with the Leeds University Union Chemical Society was held at 6.15 p.m.on Friday February 14th 1964 in the Lecture Theatre The University Leeds. The Chair was taken by the Chairman of the North of England Section Mr. C. J. House B.Sc. A.R.C.S. F.R.I.C. The following paper was presented and discussed “Hydrolytic Studies of Phosphorus Compounds Using Chromatographic Methods,” by F. H. Pollard D.Sc. Ph.D. SCOTTISH SECTION THE twenty-ninth Annual General Meeting of the Section was held at 1.45 p.m. on Friday January 24th 1964 a t More’s Hotel India Street Glasgow C.2. The Chair was taken by the Chairman of the Section Dr. R. A. Chalmers B.Sc. The following office bearers were elected for the forthcoming year Chairman-Dr. R.A. Chalmers. Vice-Chairmavt-Mr. J. K. McLellan. Hon. Secretary and Treasurer-Mr. J. W. Murfin Boots Pure Drug Co. Ltd. Airdrie Works Airdrie Lanarkshire. Menzbers of Committee-Dr. D. M. W. Anderson Mi-. W. Dunnett Ah-. J. W. Erskine Dr. J. A. Hunter Mr. J. C. Jack and Mr. A. F. Williams. Mr. J. S. Foster and Mr. R. A. Sutter were re-apyointed as Hon. Auditors. WESTERN SECTION THE ninth Ai-inual General Meeting of the Section was held at 5.30 p.m. on Friday January loth 1964 in the Welsh College of Advanced Technology Cathays Park Cardiff. The Chair was taken by the Chairman of the Section Dr. F. H. Pollard. The following appoint- ments were mz-de for the forthcoming year Chairman-Mr. E. A. Hontoir. Vice-Chairman- Dr. L. E. Colcs. Hon. Secretary and Treaszwer-Dr. T. G. Morris Brockleigh Clevedon Avenue Sully Glamorgan. Members of Committee-Dr. D. Betteridge MI-. W. Cassidy Dr. G. V. James Dr. F. H. Follard Mr. J. D. R. Thomas and Dr. \V. J. \\‘illiams. Mr. S. Dixon and Mr. C. H. Manley were re-appointed as Hon. Auditors. The Annual General Meeting was followed by an Ordinary Meeting of the Section a t which the Chair was taken by the new Chairman of the Section Mr. E. A. Hontoir B.Sc. A.I.M. The following paper was presented and discussed “Gas-chromatographic Investiga- tions of Organometallic Compounds of Group IV Elements,” by I;. H. Pollard I>.%. Ph.D.
ISSN:0037-9697
DOI:10.1039/SA964010013b
出版商:RSC
年代:1964
数据来源: RSC
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The assay of penicillins |
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Proceedings of the Society for Analytical Chemistry,
Volume 1,
Issue 3,
1964,
Page 15-21
F. R. Batchelor,
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March 19641 THE ASSAY OF PENICILLINS 15 The Assay of Penicillins REPORT OF THE MEETING OF THE SOCIETY HELD ON JANUARY 2 9 ~ ~ 1964 A MEETING of the Society on the subject of “The Assay of Penicillins’’ was held on Wednesday January 29th 1964 at the Royal Society of Medicine London W.l as previously recorded in the February issue of the Proceedings (p. 9). The five papers summarised below were presented and discussed. In his introduction he recalled that although this was the first time the Society itself had held a meeting in the Barnes Hall of the Royal Society of Medicine two of the constituent Groups of the Society had met in that same Hall to hear papers on Physical Methods andBiologica1 Methods of Penicillin Assay and by a coincidence that had only just been drawn to his attention that meeting had been held 16 years ago to the very day.On that occasion Sir Alexander Fleming had opened the discussion of the Biological Methods papers. The President Dr. D. C. Garratt Hon.M.P.S. F.R.I.C. occupied the Chair. Analytical Problems of the New Penicillins BY F. R. BATCHELOR (Beecham Research Laboratories Brockharn Park Betchworth Surrey) AIR. BATCHELOR suggested that the main problem with penicillins was perhaps not that of finding a method of assay but of adapting one of the many existing methods to the parti- cular problem in hand. There was no one assay suitable for all purposes and methods that were suitable for factory production and control were unlikely to be useful to the research worker or to the pathologist; this applied particularly to automatic methods. Some of the analytical problems encountered by the speaker while working with 6-aminopenicillanic acid illustrated this problem.The existence of the present large number of penicillins was a consequence of the dis- covery and isolation of 6-aminopenicillanic acid whose presence was first suspected during the solution of an analytical problem viz. the discrepancy between chemical and biological assay results in fermentations carried out in the absence of an added side-chain precursor. It was necessary to have some form of assay during the early work on fermentation and isolation of 6-aminopenicillanic acid and until a suit able standard became available all assays were related to benzylpenicillin. The low titre made chemical determination of 6-aminopenicillanic acid difficult even after prior removal of interfering penicillins by solvent extraction.The specific method of converting 6-aminopenicillanic acid to benzylpenicillin by reaction with phenylacetyl chloride posed many problems not least of which was the volume of sample required. However the spotting of an exact small volume (between 5 and lOp1) on filter-paper strips which were sprayed with sodium bicarbonate and then with phenylacetyl chloride in acetone proved reasonably satisfactory and was particularly useful for large numbers of samples such as eluates from ion-exchange columns. It was obviously impracticable to purify every new penicillin made from 6-aminopeni- cillanic acid and some idea of the purity was always required for evaluating the biological activity of each compound. In general it was found sufficient to use a combination of the hydroxylamine and manometric methods together with the iodimetric method on certain occasions.Paper chromatography was used extensively to check the homogeneity of the compounds and a chromatographic method involving subsequent phenylacetylation was used to estimate unconverted 6-aminopenicillanic acid. Certain compounds were found not to be amenable to particular assay methods. Complications arose with the methods involving the use of penicillinase when the penicillin was penicillinase-stable and it was worth noting that 6-aminopenicillanic acid itself was somewhat more stable to penicillinase than many penicillins mainly because the optimum pH for the penicillinase reaction was different. 6-Aminopenicillanic acid evolved little or no carbon dioxide in the manometric assay and electrometric titrations showed that this was due to the 6-amino group which was very weak (pK = 51) becoming much stronger (pK = 8.9) when the p-lactam ring was opened.When several a-halogen-substituted penicilhns were examined it was found that hydrolysis of the p-lactam ring by penicillinase made the halogen labile and in the manometric assay this led to a second molar equivalent of carbon dioxide being evolved. 16 PENICILLIN ASSAYS BY CHEMICAL METHODS [Yroc. SOC. Anal. Chew. Some of the assay problems that arose with 6-aminopenicillanic acid were later explained by the fact that it formed an adduct with carbon dioxide; this adduct then underwent a re- arrangement into 8-hydroxypenillic acid. This made it particularly important to remove the mycelium immediately after taking samples of fermentation mixtures and it also meant that the use of sodium bicarbonate as a mild neutralising agent for 6-aminopenicillanic acid in acid solutions was particularly unfortunate.Certain of the new penicillins such as phenethicillin were produced as mixtures of two diastereoisomers and it was necessary to estimate their relative proportions. Although attempts had been made to use chromatographic methods the only satisfactory way seemed to be a differential biological assay. During clinical evaluation of the penicillins it became apparent that most of those at present available could give rise to biologically active metabolites in both urine and serum. This clearly cast doubt on blood-level determinations unless it could be shown either that the metabolite was present in only very small amounts or that it had both the same anti- bacterial activity and the same dose - response relationship as the parent compound.Uiochemical studies particularly those involving- the enzymes penicillinase and penicillin amidasc required specifically adapted methods. Often this meant a quick simple method with high specificity and sensitivity rather than one of great accurac!-. It was also worth bearing in mind that exact timing might he more important than csac'c measurement of \rolume. Further accuracy might have to be sacrificed as in the detection and estimation of low orders of penicillin amidase activity where prior chromatographic separation o f 6- aminopenicillanic acid from penicillin was essential. DISCUSSIOK T H E question of bringing official assays of the penicillins into line uith neuw knowledge was raised but no official methods had been laid down under the Therapeutic Substances Kegulations.Biological chemical or physical methods could be used for the penicillins. Tt was left to the manufacturer to justify the particular method he had used. The official British Pharmacopoeia methods were the iodimeti-ic assay for b,cnz~~lpenicillin and the alkalimetric assay for methicillin. -1lthough the method was not included in the British Pharmacopoeia the purity of the penicillins could be checked ti!- radioactive tracer techniques. Jf'ith regard to the activity of metabolites o f the penicillins in urine cloxacillin had been examined in most detail the metabolite being isolated with a puritJ- of about $0 per cent.Xo evidence of difference in activity on a weight basis between the penicillin and its metabolite was found. The metabolite was penicillinase-stable as \vas the parent com- pound and with six different assay organisms gave a similar log dose - response slope to that of cloxacillin. With phenethicillin although the metabolite itself had not been isolated i t was found to have an activity - weight relationship similar t o that of the parent compound. So far no metabolites with a greatly enhanced activity - weight ratio had been found. Dr. G. E. Foster Mr. J. TIV. Lightbown and Dr. R. R. Goodall contributed to the discussion on this paper. It was found in blood and urine in roughly similar ratios. Penicillin. Assays by Cheniicfil lllaethods BY K. K. &3ODALL (Impevial Chemical Industvies L t d .Phnvmaceuiicnl Di7’isio17 -4 lderljl Pcri~li Cheshir?) DR. GOODALL said that the ideal chemical assay should discount the effect both of “blank” impurities and of any contribution from related penicillins; it should be suitable for mass-production techniques and the standard deviation should approach 1 per cent. To obtain selectivity in the analysis of crude products such as fermentation liquors two stages were necessary. The first comprised a reaction characteristic of the penicillin nucleus ; the second involved quantitative determination of the derivative. There was always a blank arising from other components of the liquor so that these assays were based on the difference between blank and test result effected by the chosen reaction. Published results which re- lated mainly to early fermentations showing less than 5000 u.per ml quoted standard devia- tions of about 2-5 per cent.; the blank contribution could account for half of this deviation. March 1964; PmiIcII,rm ASSAYS BY CHEMICAL METHODS 17 The routine assays most generally adopted were ( a ) by penicillinase or alkaline conversion to penicilloic acid and subsequent iodimetry (it should be noted that some penicillin types were relatively more resistant to penicillinase) ( b ) by conversion to the hydroxamic acid which was determined photometrically as the red ferric complex and (c) by alkaline conversion to penicilloic acid which reduced arsenomolybdate to molybdenum blue. Methods ( a ) and ( b ) were directly applicable to fermentation liquor without prior extrac- tion; method (c) required extraction presumably to avoid a turbidity that could be due to other constituents of the broth.The iodimetric method (a) had been widely adopted for the assaj- of benzyl- and phenoxymethyl-penicillins. The absorption of iodine by penicilloic acid was verj. favourable (about 9 equivalents per mole) and the alreadv sensitive iodimetric assay could have its sensitivity increased even further by photometry of the starch - iodide complex at about 600 mp. The ferric hydroxamic acid complex did not have a high light absorption but its colour was sufficiently intense for most applications. However if turbidity appeared before or during the initial hydroxamation it might not be possible to minimise interference by dilution. Xevertheless it was often possible to extract the hg-drosamic acid into a polar sol\-ent and to form the ferric complex in the solvent extract.Method (c) utilised the highly sensitive molybdenum-blue test. In manufacture fermentation liquors usually contained oi’er 00 per cent. of the required penicillin and the routine was to determine the total penicillins. The proportion of the various penicillins that might be present in the liquor or in derived salts could be found by paper chromatography. The most accurate method for determining ;L specific penicillin was bj. dilution with carbon-14-labelled isotopic penicillin. 14C-benzylpenicillin could be prepared from the commercially available C,H5CH214COOH b j ~ conversion to the acid chloride and reaction with 6-aminopenicilloic acid. C,H,O1!CCH2COOH could be prepared conveniently from phenol and Br14CH2COOH.After crystallisation to constant radioactivity and precise standardisation by taking means of several counts these isotopic penicillins could be used at a con\-enient activity for the isotopic dilution assaj- of whole or filtered fermentation liquor. Dr. (ioodall said that he had in this way determined the I’henor~ineth!-lpenicillin content of whole broth to within & 1 per cent. .Lhe routine assays (a) (h) and (c) enumerated a b o \ ~ could be partl5- or totally mech- nised bj7 using commercially available apparatus. ’The cost of this would be justified if more than about 250 assays were required each week. ? D IS c li s s I o r\; I.H I.. possibility of using nuclear magnetic resonance f o r the determination of the penicillins in the presence of one another was suggested ; benzylpenicillin and phciiox~tnethylpeiiicillin which were water soluble had given well separated peaks by this method.comparison of isotope-dilution techniques utilising deuterated phen)rlacetic acid and infrared measurement with radioactive techniques utilising carbon-14 would also be of interest. Deuterated penicillin had been used in the United States of America for isotope-dilution assay before carbon-14 was used but there was always the possibility of thc deuterium exchanging with water. In the iodimetric method the use of the starch complex \\-as recommended ; the assay was then extremely sensitive and might be used for determining levels of residual benzyl- penicillin in milk. The problem of running a standard together lvith the sample as required by the British Pharmacopoeia was raised and i t was suggested that the method might be improved by the use of a buffer as the uptake of iodine was dependent on pH.In Ur. Goodall’s opinion the number of equivalents of iodine taken up by benzyl- and phenoxymethyl-penicillins was to some degree a function o f the conditions chosen and therefore it was sound analytical practice to run standards simultaneously. In automatic assay. 40 samples per hour were run with 6 standard levels to form the slope. Huffer a t a pH of about 6 was used ; the penicilloic acid was buffered to a pH of about 4.6 and then samples were put into the machine. This technique differed slightly from that of manual assay. S o information was available on the chemical assay described in ,\merican literature in which penicillins were converted to mercury salts o f penicillenic acid ancl measured spectrophotometrically.The President (Dr. Garratt) Dr. J . E. Page Mr. F. 13. Batchelor ancl Mr. J. W Lightbown took part in this discussion. 18 USE AND MISUSE OF MICROBIOLOGICAL DETERMINATION [Proc. SOC. Anal. Cheuvz. LJse and Misuse of Microbiological Determination of Penicillins BY J. T. SMITH (Department of Bacteriology Guy's Hospital Medical School London S.E. 1) DR. SMITH said that microbiological assay was more sensitive than any chemical method for the determination of penicillins but since it was a biological system the results were more variable. Nevertheless as it measured only antibacterial activity it was of value for investi- gating alterations of penicillin activity in vivo e.g.by protein binding. Because the method did not measure biologically inactive penicillins it was most useful for evaluating levels of penicillin activity in blood and other clinical specimens. The speaker described a modified Sarcina Zutea plate method for the assay of the penicillins in body fluids. He stated that the method was simple to use and gave a greater number of results with less precision rather than a few very precise results. The sensitivity of the method towards the penicillins varied; it was most sensitive to benzylpenicillin 0.15 pg per ml being measurable and least sensitive to phenbenicillin and cloxacillin. The sensitivity to cloxacillin could be increased from 2.9 to 0.7 pg per ml by pre-diffusion of the plates before incubation. It was important to use the correct diluting fluid in experimental determinations of the levelin tissues.For research work homologous serum should be used in the assay of serum levels. For a comparison of two penicillins a large enough but not too large group of people should be used (about 12); with a large enough group the serum binding had an average effect and pooled serum could be used for diluting the standards. Bovine serum albumin could be used in place of serum for some penicillins if it was adjusted to the correct concentra- tion for each penicillin. Caution was needed in interpreting results of assays when a metabolite with activity against the test organisms was known to be present. Microbiological assay was often misused in the estimation of rates of destruction of the penicillins by enzymes as all methods that stopped these reactions also inhibited growth of the indicator organism.Cooling merely slowed the reaction to an extent dependent on the activation energy of the enzyme. The rate at which an enzyme with an apparent activation energy of 8000 calories per mole would destroy a substrate at 0" C was 15 to 19 per cent. of the rate at 37" C but if the apparent activation energy was 4000 calories per mole as it was for many penicillinases from Gram-negative bacteria the rate at 0" C was as high as about 50 per cent. of the rate at 37" C. DISCUSSION THE error usually found with the method described was not expected to be within narrow limits. Dr. Smith expressed the opinion that in the estimation of levels in blood in which the penicillin concentration was so variable from subject to subject i t did not matter i€ the method was somewhat crude.The Assay of Penicillins in Body Fluids BY JILLIAN M. BOND (National Institute for Medical Research M i l l H i l l London iV. W . 7) DR. BOND said that penicillins were determined in body fluids by biological assay by means of the plate-diffusion technique described by Lightbown and Sulitzeanu in 1957. This method in which a particularly sensitive strain of Sarcina Zutea was used had replaced the many earlier methods of assaying in tissue fluids which were mainly dilution assays often involving micro-techniques. The assay of penicillins in serum was complicated by the fact that penicillins were bound to serum proteins the degree of binding varying with the type of penicillin. The bound complex was inactive but activity was not destroyed; it was recovered when the loosely held complex was broken down.To overcome the effect of binding on assays it was necessary to estimate the total antibiotic in a serum sample by diluting the assay standards in serum from the same individual as the sample i.e. in homologous serum. The use of pooled human serum or bovine albumin as diluent for the standards was subject to criticism since it did not take into account variations in the degree of binding between individuals which had been found to exist with certain penicillins. March 19641 THE ASSAY OF PENICILLINS I N BODY FLUIDS 19 To find the percentage serum binding of a sample it was necessary to estimate inde- pendently the level of free unbound antibiotic present. A technique for doing this by filtration of serum through dialysis membrane with negative pressure was described.The amount of penicillin bound to protein i.e. the difference between total and free levels was expressed as a percentage of the total level. Relatively few details were available of penicillin levels in tissue fluids and many of those given in the literature did not take into account the possibility of binding of the penicillins to tissue protein. There was some evidence that the degree of binding was considerably less in the tissues than in serum. The assay of penicillins in urine and bile had been complicated by recent evidence that most penicillins were metabolised in the body and that the active material present in bile and urine was considerably different to the original parent material owing to the presence of one or more new biologically active components.These components could be separated chromatographically in an ether - water partition system. Assays of metabolised material against the parent material were invalid because of the dissimilarity of test and standard similarity of test and standard being one of the assumptions essential to the fundamental validity of all biological assays. Thus any potencies and limits of error calculated from such assays had no meaning other than in the specific conditions of the experiment. Much more work was needed to separate and identify these metabolites. Meanwhile if invalid assays had to be made their severe limitations should be appreciated. The fact that there was increasing evidence that metabolites of a t least some of the pencillins were present in the blood as well as in bile and urine threw doubt on the validity and meaning of assays of serum levels made by current methods.D I scu s SI ON THE question of the assay of residual penicillin in milk was raised. It was pointed out that a number of techniques had been proposed by official sources; they varied con- siderably and the problem lay in deciding which was best. It was stated that the Savcina Zutea assay could be used satisfactorily and that the degree of binding to protein appeared to be small and could be ignored. The suggestion of adding penicillinase to milk might enable it to fulfil the legal requirements but it would not remove the danger of sensitisation t o the degradation products of penicillin that would still be present. In the assay of penicillins in serum only the use of homologous serum as diluent for standards would give the correct total penicillin level for individual samples.If the requirement was only a mean total serum level for a penicillin pooled serum could be satisfactorily used provided the work was done with a large enough groups of subjects. The binding of benzylpenicillin was greater when it was determined by the filtration technique than when it was measured by electrophoresis and assay against standards in buffer. The latter method did not determine the true free level owing to some dissociation of the penicillin - protein complex during the diffusion in the assay. It was stated that metabolites had been detected from all marketed penicillins including benzylpenicillin except ampicillin and methicillin ; the apparent exceptions might be due to present chromatographic methods not being adequate for the separation of their metabolites.The problem of assay might be overcome by chromatography of urine samples and estimation of the metabolites qualitatively by the iodine-spray technique or quantitatively by cutting out the spots eluting them and measuring the penicillin by the micro-iodimetric method. It was not known if the binding capacity of an individual serum varied from time to time; a reasonable precaution was to take the serum to be used as diluent at as nearly as possible the same time as the samples were taken for assay. Dilution with phosphate buffer would dissociate the penicillin - protein complex but the degree of dilution necessary to give complete dissociation would be so great that the levels after dilution might well be below the sensitivity of the assay.An example of more activity being recovered from an animal than had been ad- ministered was mentioned. In explanation it was stated that this had occurred in tissue distribution studies of cloxacillin in rats. Discrepancies had been found when the caecal contents were assayed by different test organisms owing to the formation of a metabolite with considerably greater activity for Savcina Iutea than for Staph. auveus. 20 ANALYSIS OF THE PENICILLINS AS THERAPEUTIC AGEXTS LProc. SOC. Anal. C'lzeni. In answer to Ilr. 3. G. Heatley who asked about the use o f Sephadex to estimate the xmount of protein binding it was pointed out that this method had only been used with much higher concentrations of penicillin than the normal therapeutic levels.Mr. G. Syltes Dr. J . T. Smith Mr. J . M T . Lightbown I>r. Garratt Xlr. R. Sutherland Mr. P. G. 13. hTaylor Mr. F. I<. Batchelor Dr. G. E. Foster and Mr. 1'. .&cretl also took part in the discussion of this paper. Analysis of tlic Penicillins as Therapeutic Agents DR. STEWART said that in recent years the gioap of antibiotics knowi1 as the pencillins or p-lactam antibiotics had increased in number rnnge ailtl el'fectiveness fulfilling prophecies to this effect made by Sheehan in 1953 and by Chxin in 1960. ?'he number of bacterial strains sensitive to one or other of the penicillins had nmv increased considerablj- from the pj.ogenic cocci and spirochaetes that were sensitil-e to the original penicillins a ~ d now included the penicillinase-producing staphvlococci and coliform bacilli.Bacteria had one m-ain line of defence against penicillins in the prodation of inxtiixting enzymes. Conventional assays of sensitivity were liable to be 17itiated unless these were taken into account. For instance man) such tests werc performed routinel?. in hospital laboratories with blotting-paper discs impregnated with mtibiotic. Tested in this waj- against penicillin G many P-lactamase-forming strains of Stnp!i. a w e u s a.ppexed to be sensitive for the anti- biotic could diffuse and kill many of the organisms beiore the enzyme \$-as formed. Metliicillin and the isoxazoles were not of course affected bj this r?.nd staph?-lococci showed a normal distribution in dose - response relationship quite different to the bimodal distribution o f bcnzylpenicillin.The iatter which acted on the CO NH linkage in the side chain were more common among colifornis but were less powerful than 8-lactamases which opened t h e lxctam ring. possible howel-er to find strains of coliforms that were highljr resistant to all form. of penicillin but did not seem to form either type of enzyme. ,After oral dosagc with an enz!me thc normal flora was suppressed and the oropharyns could become colonised bj. enz!-me-producing coli- forms capable of destroying the drug. These organisms could gain access to t!ic site of thc. sensitive pathogen e.g. the lung. One criterion of efficiency for any antibiotic was the concentration attainable in infected tissue. The penicillins diffused uniformly via the capillaries into the tissues so reaching all sites of infection except avascular lesions.It was disappointing that none of the new penicillins had been able to penetrate either these tissue barriers or the blood - brain barrier to the cerebrospinal fluid. Penicillins were advantageously concentrated in both urine and bile during their rapid excretion which made them effecti1Te agents in urinarj- andbiliary infections. In this connection the failure of ampicillin to cure chronic carriers of SnlmoizelZa could be explained by the fact that these infections were usuall!. confined to the lower ileum and being well absorbed ampicillin might not reach this area. Penicillins a.s a class were singularly devoid of direct toxicity and it was to be hoped that changes in side-chain structure of the moleculc would not detract from this property.For example the recent naphthalene derivatives saggested this possibility. The metabolites of lrarious penicillins found in the urine and bile should be examined for toxic properties although there had been no suggestion of this occurring so far. An important indirect form of toxicity was the hivpersensitivity to penicillin developed in certain individuals. Unfortunately cross-allergenicity occurred between all known peni- cillins. Since 6-aminopenicillanic acid appeared to be a factor in antigenicity side-chain modifications seemed unlikely to overcome this but changes in the p-lactam nucleus as in the cephalosporins might be a means of overcoming the problem. The penicillinases could now be divided into ,t-lactamases and amidases.It Toxicity was a limiting factor in the usefulness of any drug. March 19641 PAPERS ACCEPTED FOR PUBLICXTIOX DISCUSSION THE difficulties that might arise in using discs for sensitivity testing were discussed. The zone diameters obtained were related to the inoculum size and with some penicillins the size of the colony a t the zone edge might be an important factor in interpreting results for clinical application. There could be large differences in inoculum size used in different hospitals and commercial discs sometimes varied in strength for a given antibiotic e.g. from 1 to 10 rug for penicillin G. Dr. Stewart was asked about the source of the Gram-negative amidase producers. Many amidase producers studied by one group of workers were non-clinical saprophytes nith the exception of one Pyoteus strain. The enzymes produced by these saprophytes \\.ere mainly active a t pH 9-0 but still split penicillin a t pH 7.0. The amidase producers mentioned by Dr. Stewart were from human sources niostly from lesions and their enzymes were active a t yH 6 to 7 . American workers had recentlgr found amidase producers from similar clinical sources. I t was impossible to be sure that strains of Pyotezts and F I . colz isolated during the co~irse o f treatment were not due to re-infection. Immunological techniques had not been used to study these strains ; only the biochemical reactions and sensitivity patterns had heen followed. A h - . L. Jeffries Mr. F. R. Ratchelor and Rfr. I<. Sntherland contributetl to this tliscussion. 21
ISSN:0037-9697
DOI:10.1039/SA9640100015
出版商:RSC
年代:1964
数据来源: RSC
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Papers accepted for publication inThe Analyst |
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Proceedings of the Society for Analytical Chemistry,
Volume 1,
Issue 3,
1964,
Page 21-21
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March 19641 PAPERS ACCEPTED FOR PUBLICXTIOS 21 Papers -4ccepted for Publication in The Analyst ,. 1 HE lolloiving papers have been accepted for publication in 7‘7zr =1 nalJlst and are expected to appear in the near future. ’ ‘Spcctrophotometric Determination of Iron and Aluminium in Lea\-es of the Rubber Tree (Hewn bvaziliemis),” by K. R. Middleton. “&\n Improved Method for the Identification of Furfuraldehj.de in HjTdrocarbon Oil ’ ’ 13~- J. F. Palframan and B. A. Rose. “‘l‘he Titrimetric and Spectrophotometric Determination of the Oxidking Capacitj- of Manganese Compounds,” by A. D. Wilson. “The Chromatographic Detection and Determination of Orgaiio-chlorine Herbicidcs in Soil and IVater,” by D. C. Abbott H. Egan E. \r7. Hammond and J. Thomson. “Spectrophotometric Determination of Vitamin D in Presence of T‘itaniin A\,’’ by K.K . Rarua and M. V. K. Rao. “Iieco\~ery of Malathion Residues from Pimento,” by D. G. Rowlands. ’ “The Determination of Some Triazine Herbicides by Gas - Liquid Chromatographj- Renfield and E. D. Chilwell. “The L4bsorptiometric Determination of Iron in Boiler Feed-water. Part I. Method “The -4bsorptiometric Determination of Iron in Boiler Feed-ivater. “The Determination of the Capsaicin Content of Capsicum and its Preparations.” ivith Particular Reference to Atraton in Soil,” by C. for Determining ‘Reactive’ Iron,” by A. L. IVilson. for Dissolving “on-reactive’ Iron,” by A. L. Wilson. -4 Report prepared by the Joint Committee of the Pharmaceutical Society and the Society for Analytical Chemistry on Methods of Assay of Crude Drugs. “.In Absorptiometric Method for Determining Ammonia in Hoiler Feed-water,” b!- J. Part 11. Method? Tetlow and A. L. Wilson.
ISSN:0037-9697
DOI:10.1039/SA9640100021
出版商:RSC
年代:1964
数据来源: RSC
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Publications received |
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Proceedings of the Society for Analytical Chemistry,
Volume 1,
Issue 3,
1964,
Page 22-23
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22 PUBLICATIONS RECEIVED [Proc. SOC. Anal. Cheuut. Publications Received The publications listed below have been received by the Editor of The Analyst in which journal Book Reviews will continue to appear. OILS AND FATS. By J. W. COPIUS PEEREBOOM. Pp. xii + 157. The Netherlands Centrum Voor Landbouwpublikaties en Landbouwdocumentatie. 1963. Price Dfl 11.25. THEORIE UND PRAXIS DER GRAVIMETRISCHEN ANALYSE. Part I. THEOKETISCHER TEIL. By Dr. LASZL~ ERDEY. Pp. 382. Budapest Xkadkmiai Kiadh. 1964. Price $9.00. Edited by J . FRIEUEL and A. GUINIER. New York and -Amsterdam W. A. Benjamin Znc. 1963. Price $19.75. HANDBUCH DER PAPIERCHROMATOGRAPHIE. Edited by I. M. HAIS and K. MAEEK. Part I. GRUNDLAGEN UND TECHNIK. Pp. xvi + 1069. Jena Veb Gustav Fischer Verlag. 1963. Price DM 72.40; 123s. 7d. HAXDRUCH DER PAPIERCHROMATOGRAPHIE.Edited by I. M. HAIS and K. MACEK. Part 111. BIBLIOGRAPHIE 1957-1960 UXD ANWENDUXGEN. Jena ’I’eb Gustav Fischer Verlag. 1963. Price DM 40.90; 69s. 10d. Editor F. U’. GIBBS with an editorial advisory board. Pp. 60. London The Royal Institute of Chemistry. Xnnual subscription (four issues per year) 40s. ; $7. A New Journal CHROMATOGRAPHIC STEROL ANALYSIS AS APPLIED TO THE INVESTIGATION OF ATILK FAT AKD OTHER METALLIC SOLID SOLUTIONS A SYMPOSIUM ON THEIR ELECTRONIC AXD ATOMIC STRUCTURE. Pp. xiv + 674. Pp. xx + 700. EDUCATION IN CHEMISTRY. Vol. 1 No. 1 January 1964. TRACE ANALYSIS OF SEMICONDUCTOR MATERIALS. Edited by J . PAUL CALI. Pp. x + 282. STANDARD METHODS OF THE OILS AND FATS DIVISION OF THE I.U.P.A.C. (Text Pp. xxii + 190. London Butterworth & Co.(Publishers) Ltd. Oxford London New York and Paris Pergamon Press. in English and French). 1964. Price 50s. 1964. Price 70s. Fifth Edition. Published as a Supplement to Pure and ,Applied Chemistry THE QUANTITATIVE ANALYSIS OF DRUGS. By D. C. GARRATT D.Sc. Ph.D. Hon. M.P.S. F.R.1 .C. i4ssisted by L. BREALEY B.Sc. Ph.D. F.R.I.C. C. A. JOHKSON B.Sc. B.Pharm. F.P.S. F.R.I.C. K. L. SMITH M.P.S. and G. SYKES M.Sc. F.R.I.C. Pp. xiv + 925. London Chapman & Hall Ltd. 1964. Price 126s. I’RAKTIKUM DER QUANTITATIVEN ANORGANISCHEK ANALYSE. By HERMANN Lux. Fourth Edition. Pp. viii + 204. Munchen J . F. Bergmann. Berlin Gottingen and Heidelberg Springer-Verlag. 1963. Price DM 15.80. Third Edition. March 19643 NOTICES 23 DATA FOR X-RAY ANALYSIS. Volume I. CHARTS FOR SOLUTION OF BRAGG’S EQUATIOK (d VERSUS 8 AND 28 FOR COPPER K RADIATION).Second Edition. Pp. x + 125. Holland Philips Technical Library. Distributed in U.K. and Eire by Cleaver-Hume Press Ltd. (The Macmillan Co. Ltd.) London. DATA FOR X-RAY ANALYSIS. Volume 11. CHARTS FOR SOLUTION OF BRAGG’S EQUATION (d VERSUS 8 AND 28 FOR MOLYBDENUM K COBALT K AND TUSGSTEN L RADIATIONS). By I J T ~ ~ ~ ~ ~ ~ f PARRISH and MARIAN MACK. Second Edition. P p . x + 141. Holland Philips Technical Library. Distributed in U.K. and Eire by Cleaver-Hume Press Ltd. (The ;IIacmillan Co. Ltd.) London. 1963. Price 38s. CHARTS FOR SOLUTIOS OF BRAGG’S EQUATION (d VERSUS 8 AND 28 FOR IRON K AND CHROMIUM K RADIATIONS). By WILLIAM PARRISI~ and MARIAN MACK. Second Edition. Pp. x + 137. Holland Philips Technical Library. Distributed in U.K. and Eire by Cleaver-Hume Press Ltd. (The Macmillan Co. Ltd.) London. 1963. Price 38s. By WILLIAM PARRISH and MARIAN MACK. 1963. Price 32s. DATA FOR X-RAY A 4 ~ ~ ~ ~ ~ ~ ~ . Volume 111. THERMAL PHYSICS. By PHILIP M. MORSE. Pp. xiv + 455. New York and Amsterdam W. ,4. Benjamin Inc. 1964. Price $10.50. 146. Press Ltd. (The Macmillan Co. Ltd.) London. 1963. Price 35s. Sew York and London Academic Press. 1963. Price $14.00. PRACTICAL GAMMA SPECTROMETRY. By A. J . DUIVENSTIJN and L. ,4. J. VENVERLOO. Pp. viii + Distributed in U.K. and Eire by Cleaver-Hume PROGRESS IN CHEMICAL TOXICOLOGY. Volume 1. Edited by ABRAHAM STOLMAX. Pp. xiv + 436. Holland Philips Technical Library.
ISSN:0037-9697
DOI:10.1039/SA964010022b
出版商:RSC
年代:1964
数据来源: RSC
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Notices |
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Proceedings of the Society for Analytical Chemistry,
Volume 1,
Issue 3,
1964,
Page 23-23
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March 19643 NOTICES 23 Notices BRITISH STANDARDS INSTITUTION DRAFT SPECIFICATIONS A FEW copies of the following draft specifications issued for comment only are available to members of the Society and can be obtained from the Secretary The Society for L4nalytical Chemistry 14 Belgrave Square London S.W.1. Draft Specification prepared by Sub-Committee LBC/1/5-Volumetric Glassware. Draft Specifications prepared by Sub-committee PVC/ 1/8-Chrome Pigments. D 64/901-Draft R.S. Specification for Density Bottles (Revision of B.S. 733). D 64/1202-Draft B.S. Specification for Prussian Blue for Paints (Types 1 and 2) D 64/1203-Draft B.S. Specification for Brunswick or Lead Chrome Greens (Pure (Revision of B.S. 283). and Reduced) for Paints (Revision o€ B.S. 303). Draft Specification prepared by Technical Committee CIC/26-Reagent Strengths. D 64/1218-Draft B.S. Specification for Water for Laboratory Use. OPEN DAYS AT THE LABORATORY OF THE GOVERNMENT CHEMIST THE Laboratory of the Government Chemist which provides analytical investigatory and advisory services to H.M. Government Departments is to hold its first Open Days in the new Cornwall House premises on April 22nd and 23rd 1964. Tickets to visit the Laboratory can be obtained in advance from The Government Chemist Cornwall House Stamford Street London S.E.l. Applicants should state which day they would like to attend whether morning afternoon or all day.
ISSN:0037-9697
DOI:10.1039/SA9640100023
出版商:RSC
年代:1964
数据来源: RSC
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Reprints of review papers |
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Proceedings of the Society for Analytical Chemistry,
Volume 1,
Issue 3,
1964,
Page 24-24
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24 REPRINTS OF REVIEW PAPERS [Pvoc. SOC. A.lzal. Chem. Reprints of Review Papers REPRINTS of the following Review Papers published in T h e Analyst are available from the Secretary The Society for Analytical Chemistry 14 Relgrave Square London S.W. 1 (not through Trade Agents). Orders MUST be accompanied by a remittance for the correct amount made out to “Society for Analytical Chemistry.” “The Analysis of Synthetic Detergents,” by \V. B. Smith (February 1959). “The Infra-red Analysis of Solid Substances,” by G. Ihyckaerts (April 1959). “X-ray Fluorescence Analysis,” by F. Brown (June 1959). “Ferrous Metallurgical Analysis,” by B. Bagshawe (August 1959). “Zone Melting with Some Comments on its Analytical Potentialities,” by E. I?. G. Herington “The Analytical Chemistry of Zirconium,” by G.W. C. Milner and J . \Y. Edwards (February “Light-scattering Methods for the Chemical Characterisation of Polymers,” by F. IT Peaker “Analysis of Organo-silicon Compounds with Special Reference to Silanes and Siloxanes ” by “Flame-photometric Methods in Metallurgical Analysis,” by John -4. Dean (September 1960). “The Oxygen Flask Method,” by 24. M. G. Macdonald (January 1961). “Analytical Chemistry of Beryllium,” by L. E. Sinythe and R. X. IZ’hittem (February 1961). “Determination of Residual Organo-phosphorus Insecticides in Foodstuffs,” by E. D. Chilwell “Biological Standardisation and the Analyst,” by J . IT. Lightbown (AApril 1961). Price 5s. “The Toxicology of Nitrates and Nitrites with Particular Reference to the Potability of \\‘ater “Coulometric Methods in Analysis,” by D.T. Lewis (‘Iugust 1961). “Emission Spectroscopy of Solutions,” by L. G. Young (January 1962). “Analytical Applications of the Mercury Electrode,” by J . X. Page J . A . Maxwell and I<. P. “The Determination of Tantalum and Niobum,” by &I. H. Cockbill (*\upst 1962). Price 5s. “Classification of Methods for Determining Particle Size,” by the Particle Size Analysis Sub- “Methods of Separation of Long-chain Unsaturated Fatty *icids,” by *A. T. James (August “Beer’s Law and its TJse in ,Analysis,” by G. F. Lothian (September 1963). “,I Review of the Methods Available for the Detection and Determination of Small Amounts “Circular Dichroism,” by R. D. Gillard (November 1963). “Information Retrieval in the ,Analytical Laboratory,” by 11. I<. Curry (November 1963). “Thermogravimetric Analysis,” by A.\V. Coats and J . P. Redfern (December 1963). Price 5s. “Some Analytical Problems Involved in Determining the Structure of Proteins and Peptides,” Reprints of Review Papers Not o n this list are n o l o q e r available fyow the Society. Many back numbers of The Analyst are still available and may be brought from Messrs. W. Heffer & Sons Ltd. 3-4 Petty Cury Cambridge price 15s. plus 9d. postage. Price 2s. 6d. I’rice 2s. 6d. Price 2s. 6d. Price 5s. (December 1959). Price 5s. 1960). Price 5s. (April 1960). Price 5s. J . C. R. Smith (July 1960). Price 5s. Price 5s. Price 5s. Price 5s. and G. S. Hartley (March 1961). Price 5s. Supplies,” by E. H. \Y. J . Burden (July 1961). Price 2s. 6d. Price 5s. Price 5s. Graham (April 1962). Price 5s. Committee of the Analytical Methods Committee (March 1963). 1963). Price 5s. Price 5s. Price 5s. of Cyanide,” by I,. S. Bark and H. G. Higson (October 1963). I’rice 5s. Price 2s. 6d. T’rice 2s. 6d. by Derek G. Smyth and D. I;. Elliott (February 1964). Price 5s.
ISSN:0037-9697
DOI:10.1039/SA9640100024
出版商:RSC
年代:1964
数据来源: RSC
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