THE QUANTITATIVE ANALYSIS OF DRUGS

Chapman and Hall International Edition

THE

QUANTITATIVE ANALYSIS

OF DRUGS

by

D. C. GARRATT D.Se. (Lond.), Ph.D., Hon. lVLP.S., F.R.I.C.

Chief Analyst, Boots Pure Drug Co. Ltd.

Assisted by

L. BREALEY, B.Sc., Ph.D., F.R.I.C. (Physical Assays)

C. A. JOH~SO~, B.Sc., B.Pharm., F.P.S., F.R.I.C. (Chemical Assays)

K. L. S:VIITH, :\1.P.S. (Bio-Assay<)

C; SYKES, :\I.Sc., F.R.I.C. (c11icrobiology)

THIRD EDITION

CH:'\PlVIAN & HALL LTD

I I ~EW FETTER LANE, LONDON EC4-

TOPPA~ COMPANY, LIMITED

First Published 1937 under the title

DRUGS AND GALENICALS:

THEIR QUANTITATIVE ANALYSIS

Second edition 1955 Third edition 1964

© D. C. Garratt 1964

Catalogue number 4/526/75

Original English Language Edition published by CHAPMA~ & Hall Ltd. London EC 4

No part of it may be duplicated or reproduced in any manner without written permission from the publisher.

Distribution or sale of this Edition is authorized only to TOPPAN COMPANY, LIMITED, TOKYO,JAPAN in: A(~hanistan, Bangladesh, Brunei, Burma, Cambodia, Hong Kong, India, Indonesia, Japan, Korea, Laos, Macao, Malaysia, Nepal, Pakistan, Philippines, Singapore, Sri Lanka, Taiwan, Thailand and Vietnam. Available in other countries only through CHAPMAN & HALL LTD.

ISBN-13: 978-0-412-14810-1 DOl: 10.1007/978-1-4613-3380-7

e-ISBN-13: 978-1-4613-3380-7

PREFACE TO THIRD EDITION In the present volume-as in previous editions--the intention of the

author is to survey comprehensively all medicinal drugs commonly in use together with their pharmaceutical preparations.

The last five years has seen a very rapid advance in the field of pharma­ceutical analysis and the need for revision of the previous edition has become evident. Further, the claims for incorporation of all methods used in the examination of drugs-chemical, physical, microbiological and biological-cannot be denied any longer since each type of determination is sometimes necessary for the adequate control of medicinal preparations.

The author's practice in this book has always been to select from ex­perience those methods likely to prove most serviceable rather than pro­duce a compendium of all published methods. Because of the rapid increase in the techniques available for pharmaceutical analysis, the need for specialisation has grown and the author has realised the impractic­ability of keeping in touch with all the practical details which are so valuable to the analyst. To overcome this difficulty and to enhance the value of the book, he has obtained the collaboration of specialist colleagues in the various fields of activity now included in the book. Each contributor is, in the author's opinion, an authority in his sphere of work and the author's thanks are due to Dr. L. Brealey (physical assays), Mr. C. A. Johnson (chemical assays), :\1r. K. L. Smith (bio-assays) and Mr. G. Sykes (microbiology) for their painstaking work; inevitably the greatest burden fell on 1\1r. Johnson who devoted much time and energy to the task.

About one half of the previous edition has been completely re-written, a few monographs have been deleted and the remainder of the book has been revised; a considerable amount of new material has been added and many new appendices avoid repetition in the main text. A considerable amount of explTlmental work has been necessary to adopt colorimetric methods to the Il~t' of spectrophotometric measurements at specific wavelengths.

The various pharmacopceias and codices have a major influence on the control of the purity of drugs and any textbook on drug analysis must take cognisance of the methods in current official publications. The necessarily frequent publication of new pharmacopceias is occasioned by the new drugs available rather than by advances in analytical chemistry; this edition is correlated \\ith the British PharmacopCEia 1958 and the United States Pharmacopeia XVI, but since it includes the latest trends in analyti­cal techniques its contents should cover official methods for quantitative

v

PREFACE TO THIRD EDITION

determinations in future editions of official books. However, since stand­ards may become out-of-date 'it has been decided not to include them in this edition.

The author again desires to thank the General Medical Council for permission to include material from the British Pharmacopreia and the Pharmaceutical Society of Great Britain for permission to include material from the British Pharmaceutical Codex. The Association of Official Agri­cultural Chemists has also granted permission to utilise information from their Official Methods of Analysis.

The author wishes to thank numerous journals, particularly The Analyst and The Journal of Pharmacy and Pharmacology for permission to publish information. The Society for Analytical Chemistry has also been generous in permitting access to its Analytical Methods Committee reports when in the press.

During revision the author has had the benefit of assistance of col­leagues other than those already mentioned. He wishes to thank Mr. W. L. Sheppard, B.Sc., F.R.I.e., for the revised monographs on Vitamin A and Vitamin D, Mr. P. G. Marshall, M.A., for the appendix on Infra-red Spectroscopy, Mr. G. Brewer, A.I.L., for checking the references, Mr. K. Hazzledine for line drawings and numerous associates for personal contributions; these include Messrs. P. Atherton, A.R.I.C., D. A. Elvidge, B.Sc., F.R.I.e., W. H. Harper, and Miss N. F. Mullholland, B.Sc. Others are acknowledged in the text.

Finally, the author's grateful thanks are given to Miss C. King, B.Sc., for preparation of the index, for very patient proof-reading and assistance in preserving uniformity of style and also to Miss I. Ladden, B.Pharm., for compilation of manuscripts and proofs for the printers; their en­thusiastic heIp was invaluable.

D. C. GARRATT

VI

PREFACE TO THIRD EDITION

ABBREVIATIONS

CONTENTS

GENERAL MONOGRAPHS, ALPHABETICALLY ARRANGED AND CONSISTING

OF METHODS FOR QUANTITATIVE DETERMINATION OF THE SUBSTANCE,

ITS SA~TS, AND PREPARATIONS OF WHICH IT IS A PRINCIPAL CON-

PAGE

V

lX

STITUENT 1 SYNTHETIC ORGANIC COMPOUNDS. METHODS FOR DETERMINATION OF

SUBSTANCES NOT INCLUDED IN THE GENERAL MONOGRAPHS 700

ESSENTIAL OILS 716

OILS, FATS AND WAXES 750

ApPENDICES

I. Determination of Alcohol Content 778

II. Complexometric Titrations 786

III. Kon-aqueous Titrations 792

IV. The Oxygen-Flask Combustion Technique 796·

~Dm~~~~Wmr ~

VI. Extraneous Matter in Food and Drugs 809

VII. Microbiological Assays 813

VIII. Tests for Sterility 827 IX. Pyrogen Testing 833 X. Interpretation of Analytical Results 836

XI. Destruction of Organic Matter 851

XII. Extraction of Organic Chemicals from Viscera, etc. 859

XIII. Electrometric Titrations XIV. Flame Photometry

XV. Gas Chromatography

XVI. Infra-Red Spectroscopy

864 870

876 881

XVII. The Elimination of Emulsions 887

XVIII. Lam: and Eynon Sugar Titration Tables 888 XIX. Hinton and '\Tacara Chloramine Sucrose Corrections 889 XX. Specific Gravity of Aqueous Glycerol 890

XXI. International Atomic Weights, 1961 891 XXII. Weights and '\leasures, Conversion Tables 893

GENERAL INDEX 895 Vll

The use of portions of the text of the United States Pharmacopeia, XVI Revision, official October 1, 1960, is by permission received from the Board of Trustees of the United States Pharmacopeial Convention. The said Board is not responsible for any inaccuracies of the text thus used.

Permission to use portions of the text of the National Formulary, Eleventh Edition, official October 1, 1960, has been granted by the American Pharmaceutical Associa­ti~n. The American Pharmaceutical Association is not responsible for any inaccuracy of quotation, or for false im­plications that may arise by reason of the separation of excerpts from the original context.

Ylll

ABBREVIATIONS

A.B.C.M.

A.G.A.C.

Acta Chem. Scand. Acta Pharm. Sinica

Acta Pharmacol. Toxicol.

Amer. J. Pharm. Amer. ]. Sci. Amer. Soc. Testing Materials,

Spec. Tech. Publ. Anal. Chern. Anal. Chim. Acta Analyst Ann. Appl. Bioi. Ann. Chim. Anal. et

Chim. Appl. Ann. Chim. Appl. (Roma) Annalen Antibiotics & Chemotherapy Arch. Biochem. Biophy.l. Arch. Pharm. Aui ConKr. ;Vaz. Chim. Pum

ed Appl. B.M.J. B.N.F. B.P. B.P.C. B.S. B. Vet. C. Ber.

Biochem . .r. Biometrika Boll. Chim.-Farm. Brit. J. Anasthesia Brit. ]. Ind. Med. Brit. ]. Nutrition Bul. Soc. Sti. RII(ure~ti

Bull. Narcotics

Publications

The Association of British Chemical :Vlanufacturers

:\lethods of Analysis of the Associatiol of Official Agricultural Chemists 9th edn., ( 1960)

Acta Chemica Scandinavica Acta Pharmaceutica Sinica: also known as

Yao Hsueh Hsueh Pao Acta Pharmacologica et Toxicologica.

Kobenhavn American Journal of Pharmacy American Journal of Science American Society for Testing Materials,

Special Technical Publication Analytical Chemistry Analytica Chimica Acta Analvst Ann,;ls of Applied Biology Annales de Chimie Analytique et de

Chimie Appliquee Annali di Chimica Applicata (Rom2) Annalen der Chemie, Justus Liebigs Antibiotics & Chemotherapy Archives of Biochemistry and BiophysIcs Archiv der Pharmazie Atti del Congresso Nazionale di Chimica

Pura ed Applicata British :VTedical Journal British]\; ational Formulary (1960) British Pharmacopcria (11,58) British Pharmaceutical Codex (1959) British Standard British Veterinary Codex (1953) Berichte der Deutschen Chemischen

( ;ese llschaft Biochemical J Durnal Biometrika Bollettino Chimico-Farmaceutico. Milano British Journal of Amesthesia British Journal of Industrial Medicine British Journal of Nutrition Bulctinul Societatii de Stiinte din

Bucure~ti Bulletin on Narcotics, United Nations,

I )epartment of Social Affairs

IX

ABBREVIATIONS

Bull. Sci. Pharmacol.

Bull. Soc. Chim. France C&D Geskosl. Farm. Chem. Anal. (Warsaw) Chern. & Ind. Chern. Eng. Mining Rev.

Chem. Listy Chern. Weekblad Chern. Zvesti Chemiker-Ztg. Chim. et Ind. (Paris) Chimia (Switz.) Compt. Rend.

D.A.B.

Dansk. Tidsskr. Farm. Determination of Trace

Elements, S.A.C.

Drug Standards Drugg. Circ. Dtsch. Apoth.-Ztg. Endocrinology FAO Plant Protection

Bulletin

F.D.A.

Federation Proc. Giorn. Farm. Chim.

Helv. Chim. Acta Ind. Eng. Chem. Ind. Eng. Chern., Anal. Edn.

Int. Sugar ]. ].A.O.A.C.

]. Agric. Food Chern. ]. Amer. Chern. Soc. ]. Amer. Oil Chernists' Soc.

]. Amer. Pharm. Ass.

Bulletin des Sciences Pharmacologiques. Paris

Bulletin de la Societe Chimique de France Chemist and Druggist Ceskoslovenska Farmacie Chemia Analityczna (\Varszawa) Chemistry and Industry Chemical Engineering and Mining Review.

Melbourne Chemickc Listy Chemische Weekblad Chemicke Zvesti Chemiker-Zeitung Chimie et Industrie (Paris) Chimia (Switzerland) Comptes Rendus Hebdomadaires des

Sceances de I' Academie des Sciences Deutsches Arzneibuch, 6 Ausgabe

German Pharmacopreia, 6th Edition Dansk Tidsskrift for Farmaci The Society for Analytical Chemistry.

Analytical :vIethods Committee. Trace Elements in Fertilisers and Feeding­Stuffs Sub-Committee. Determination of Trace Elements, with Special Reference to Fertilisers and Feeding­Stuffs (Cambridge), W. Hefler and Sons Ltd., 1963

Drug Standards Druggists' Circular, New York Deutsche Apotheker-Zeitung Endocrinology Food and Agriculture Organisation of the

United Nations, FAO Plant Protection Bulletin

United States Food and Drug Administration

Federation Proceedings Giornale di Farmacia, di Chimica e di

Scienze affini Helvetica Chimica Acta Industrial and Engineering Chemistry Industrial and Engineering Chemistry,

Analytical Edition International Sugar Journal Journal of the Association of Official

Agricultural Chemists Journal of Agricultural and Food Chemistry Journal of the American Chemical Society Journal of the American Oil Chemists'

Society Journal of the American Pharmaceutical

Association

x

ABBREVIATIONS

]. Amer. Pharm. Ass., Sci. Edn.

]. Appl. Chem. ]. BioI. Chem. ]. Chem. Educn. ]. Chem. Soc. ]. Chroma tog. ]. Endocrinology ]. Fed. Insts. Brewing

]. Ind. Eng. Chem.

]. Inst. Petrol. ]. Org. Chem. ]. Pharm. Chim. ]. Pharm. Pharmacal. ]. Pharm. Sci. ]. Pharmacal.

]. Roy. Soc., N .• S.W.

]. Roy. Statist. Soc., Suppl.

]. Sci. Food Agric.

]. Soc. Chem. Ind.

]. Soc. Chem. Ind., japan

Lez. Chim. Org. Microchem. j. Mikrochemie

Mikrochemie. Pregl-Festschr. Mikrochim. Acta Mitt. Dtsch. Pharm. Ges.

(pub!. in Arch. Pharm.)

N.F. Nature N aturwissenschaften P.E.O.R. Ph. I.

Pharm. Acta Helv. Pharm . .f. Pharm. Soc.

Pharm. Weekblad Pharm. Zentralhalle Pharm. Ztg.

Journal of the American Pharmaceutical Association, Scientific Edition

Journal of Applied Chemistry Journal of Biological Chemistry Journal of Chemical Education Journal of the Chemical Society Journal of Chromatography Journal of Endocrinology Journal of the Federated Institutes of

Brewing, London Journal of Industrial and Engineering

Chemistry Journal of the Institute of Petroleum Journal of Organic Chemistry Journal de Pharmacie et de Chimie Journal of Pharmacy and Pharmacology Journal of Pharmaceutical Sciences Journal of Pharmacology and Experimental

Therapeutics Journal of the Royal Society of New South

\Vales Journal of the Royal Statistical Society,

Supplement Journal of the Science of Food and

Agriculture Journal of the Society of Chemical

Industrv Journal o(the Society of Chemical Industry,

Japan Lezioni di Chimica Organica IVlicrochemical Journal l\ Iikrochemie vereinigt mit Mikrochimica

Acta Mikrochemie. Pregl-Festschrift l\1ikrochimica Acta :\litteilungen der Deutschen Pharmazeut­

ischen Gesellschaft und der Pharma­zeutischen Gesellschaft der DDR. In­cluded in Archiv der Pharmazie

:\ational Formulary XI (1960) :\"ature l\'" aturwissenschaften Perfumery and Essential Oil Record Pharmacopcea Internationalis

(I nternational Pharmacopceia) First Edition

Pharmaceutica Acta Helvetia: Pharmaceutical Journal The Pharmaceutical Society of Great

Britain Pharmaceutische Weekblad Pharmazeutische Zentralhalle Pharmazeutische Zeitung

Xl

Proc. Feigl Anniversary Symp.

Proc. Roy. Soc. (London) Pyrethrum Post Quart. ]. Pharm.

Rec. Trav. Chim.

S.A.C. S.I. Sci. Pharm. Science Soap Sanit. Chemicals Spectrochim. Acta Spice Mill Talanta Trans. Faraday Soc. U.S.P.

Y.B. Pharm. Z. Anal. Chern. Z. Angew. Chem. Z. Anorg. Chem. Z. Elektrochem. Z. Offentl. Chem. Z. Untersuch. Lebensm.

Zavod. Lab.

A [ex]D amp. At.Wt. b.p. B.S.S. cm cm- 1

O(optical) O( temperature) of oK dm E EDTA

ABBREVIATIONS

Analytical Chemistry 1962. Philip W. West et al., eds. The Proceedings of the Inter­national Symposium held at Birmingham University (U.K.), April 1962 in honour of FRITZ FEIGL to commemorate his 70th birthday. (Amsterdam), Elsevier Publish­ing Company, 1963

Proceedings of the Royal Society (London) Pvrethrum Post Q'uarterly Journal of Pharmacy and

Pharmacology Recueil des Travaux Chimiques des

Pavs-Bas Soci~ty for Analytical Chemistry Statutory Instrument Scientia Pharmaceutica Science Soap and Sanitary Chemicals Spectrochimica Acta Spice Mill Talanta Transactions of the Faraday Society Pharmacopeia of the United States XVI

(1960) Year-Book of Pharmacy Zeitschrift fUr Analytische Chemie Zeitschrift fUr Angewandte Chemie Zeitschrift fUr Anorganische Chemie Zeitschrift fUr Elektrochemie Zeitschrift fUr Offentliche Chemie Zeitschrift fUr Untersuchung der

Nahrungs- und Genussmittel sowie der Gebrauchsgegenstande

Zavodskaya Laboratoriya

General

angstrom units specific rotation ampere atomic weight boiling-point British Standard sieve centimetre wave number (frequency of radiation) angular degree degree Centigrade degree Fahrenheit degree Kelvin decimetre extinction ethylenediamine tetra-acetic acid, used

as the di-sodium salt

XII

e.m.f. f.p. g LU. In.

I lb LD50

m M m.p. rnA MeV mg ml rom mil mV Mol.Wt. ItA Ilg III N N.P.L. N.T.P. o p. p p.p.m. p.s.i. pH pK r.p.m. RF S.C.E. s.w.g. sp.gr. sq.cm. u V v 'v w/v w/w

ABBREVIATIONS

electro-motive force freezing-point gramme International Unit inch litre pound a dose lethal to 50 per cent of the

orgamsms meta molar (concentration) melting-point milliampere mega-electronvolt milligramme millilitre millimetre millimicron = 10-6 millimetre millivolt molecular weight microampere mlcrogramme microlitre nonnal (concentration) \;ational Physical Laboratory nonnal temperature and pressure ortho page para parts per million per square inch hydrogen ion exponent dissociation constant revolutions per minute relative band speed standard calomel electrode standard wire gauge specific gravity square centimetre unit volt volume in volume weIght in volume weight in weight

Xlii