Analytical Profiles of Drug Substances 18 PDF
Preview Analytical Profiles of Drug Substances 18
Analytical Profiles of Drug Substances Volume 18 Edited by Klaus Florey The Squibb Institute for Medical Research New Brunswick, New Jersey Contributing Editors Abdullah A. Al-Badr Harry G. Brittain George A. Forcier Lee T. Grady ACADEMIC PRESS, INC. Harcourt Brace Jovanovich, Publishers San Diego New York Berkeley Boston London Sydney Tokyo Toronto EDITORIAL BOARD Abdullah A. Al-Badr George A. Forcier Gerald S. Brenner Lee T. Grady Glenn A. Brewer Eugene L. Inrnan Hany G. Brittain G. Williams Martin James E. Carter John E. Zarembo Academic Press Rapid Manuscript Reproduction This book is printed on acid-free paper. @ COPYRIGHT 0 1989 BY ACADEMIC PRESS. INC. All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. ACADEMIC PRESS, INC. San Diego, California 92101 United Kingdom Edition published by ACADEMIC PRESS LIMITED 24-28 Oval Road. London NW1 7DX LIBRARY OF CONGRESS CATALOG CARD NUMBER: 89-659072 International Standard Serial Number: 0099-5428 ISBN 0-12-260818-6 (alk. paper) PRINTED IN THE UNITED STATES OF AMERICA 8 9 9 0 9 1 9 2 9 8 7 6 5 4 3 2 1 AFFILIATIONS OF EDITORS AND CONTRIBUTORS Ezzat M . Abdel-Moety, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia Abdullah A . Al-Badr, King Saud University, Riyadh 11451, Saudi Arabia Humad A. Al-Khamees, College of Pharmacy, King Saud University, Saudi Arabia Abdulrahman M . Al-Obaid, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia Khalid A . Al-Rashood, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia Khalid A. M . Al-Rashood, College of Applied Medical Sciences, King Saud University, Riyadh 11451, Saudi Arabia Fahad J . AZ-Shamrnary, College of Applied Medical Sciences, King Saud University, Riyadh 11451, Saudi Arabia Syed Laik Ali, Zentrallaboratorium Deutscher Apotheker, 6236 Eschborn, Federal Republic of Germany Said M. Buyomi, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia Ingrid Becue, Ciba-Geigy Corporation, Suffern, New York 10901 Gerald A. Brenner, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486 Glenn A . Brewer, The Squibb Institute for Medical Research, New Bruns- wick, New Jersey 08903 Hurry G . Brittain, The Squibb Institute for Medical Research, New Brunswick, New Jersey 08903 Auke Bult, Faculty of Pharmacy, State University of Utrecht, 3511 GH Utrecht, The Netherlands vii ... Vll l AFFILIATIONS OF EDITORS AND CONTRIBUTORS James E . Carter, Janssen Pharmaceutical, Piscataway, New Jersey 08854 Seham S . El-Hawary, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia Humeida A. Et-Obeid, College of Pharmacy, King Saud University, Riyadh 1145 1, Saudi Arabia Klaus Florey, The Squibb Institute for Medical Research, New Bruns- wick, New Jersey 08903 George A . Forcier, Pfizer Inc., Groton, Connecticut 06340 Lee T. Grady, The United States Pharmacopeia, Rockville, Maryland 20852 hos t J . M . Holthuis, Faculty of Pharmacy, University of Utrecht, 3511 GH Utrecht, The Netherlands Eugene L. Znman, Lilly Research Laboratories, Indianapolis, Indiana 46285 Vijay K . Kapoor, Department of Pharmaceutical Sciences, Panjab Univer- sity, Chandigarh 160014, India J . Jantina Kettenes-van den Bosch, Faculty of Pharmacy, University of Utrecht, 3511 GH Utrecht, The Netherlands Leonard J . Kostek, Pfizer Incorporated, Central Research, Groton, Con- necticut 06340 G. William Martin, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709 Mohammad Saleem Mian, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia Neelofur Abdul Aziz Mian, College of Applied Medical Sciences, King Saud University, Riyadh 11451, Saudi Arabia Farid J . Muhtadi, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia Gandharva Padmanabhan, Ciba-Geigy Corporation, Suffern, New York 10901 Mohammad Riaz, University of Michigan, Ann Arbor, Michigan 48109 James B . Smith, Ciba-Geigy Corporation, Suffern, New York 10901 Dorothy K . Wyatt, The United States Phannacopeia, Rockville, Maryland 20852 John E . Zarembo, W. H . Rorer Inc., Fort Washington, Pennsylvania 19034 Muhammad Uppal Zubair, Center for University Woman Studies, King Saud University, Riyadh 11451, Saudi Arabia PREFACE Although the official compendia define a drug substance as to identity, purity, strength, and quality, they normally do not provide other physical or chemical data, nor do they list methods of synthesis or pathways of physical or biological degradation and metabolism. Such information is scattered through the scientific literature and the files of pharmaceutical laboratories. I perceived a need to supplement the official compendial standards of drug substances with a comprehensive review of such information, and seventeen years ago, the first volume of Analytical Projiles of Drug Substances was published. That we have been able to publish one volume per year is a tribute to the diligence of the editors to solicit articles and even more so to the enthusiastic response of our authors, an international group associated with pharmaceutical firms, academic institutions, and compendial authorities. I would like to express my sincere gratitude to them for making this venture possible. Over the years, we have had queries concerning our publication policy. Our goal is to cover all drug substances of medial value, and therefore, we have welcomed any articles of interest to an individual contributor. We also have endeavored to solicit profiles of the most useful and used medicines, but many in this category still need to be profiled. Klaus Florey ANALYTICAL PROFILE OF AZINTAMIDE Ezzat M. Abdel-Moety and Hamad A . Al-Khamees Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P .O . Box 2457, Riyadh-11451, Saudi Arabia. ANALYTICAL PROFILES OF DRUG SUBSTANCES Copyright 0 1989 by Academic Press, Inc. VOLUME 18 1 All rights of reproduction in any form reserved 2 EZZAT M. ABDEL-MOETY AND HAMAD A. AL-KHAMEES CONTENTS 1. I NTRODUCT0R.Y 2. DESCRIPTION 2-1. Name 2-2. Formulae 2-3. The Chemical Abstract Registry (CAS) Number 2-4. Appearance, C,olor, Odor and Taste 2-5. Physical Characteristics 2-6. Crystal Characteristics 2-7 . Spectral Characterization 3. SYNTHESIS 4. PHARMACOLOGY 5 . THERAPEUTIC CATEGORATION AND USES 5-1. Categoration 5-2. Uses 6. TOXICOLOGY 7. STABILITY AND DEGRADATION 8. PHARMACOKINETICS 8-1. Biotransformation 8-2. Absorption 8-3. Excretion 9. METHODS OF ANALYSIS 9-1. Qualitative Methods 9-2. Quantitative Methods ACKNOWLEDGEMENT REFERENCES AZINTAMIDE 3 1. INTRODUCTORY Azintamide is a true potent choleretic drug, which is totally synthesized in 1959. The drug has the registered trade name OragallinB . In spite of the potent choleretic activity, with moderate cholepoietic action, and its wide therapeutic applications in different conditions and countries, no detailed informations about its physical, chemical, clinical, and bioavailability characteristics have been yet collectively summarized in simple presentation. The present Analytical Profile is an effort in this direction. 2. DESCRIPTION 2-1. Names 2.11. Chemical: 2-[(6-Chloro-3-pyridazinyl) thiol-N,N-diethylacetamide. Other chemical names are, N,N-diethyl-2-[6-(3- chloropyridaziny1)thiolacetamide; N,N-diethyl-2-[6-(3- chloropyridaziny1)-mercapto]acetamide; and (3-chloro-6- pyridaziny1thio)acetic acid diethylamide (1). 2 .12 . Properioritg: Oragallin, Ora-gallin, and ST 9067. Azintamide has been registered under the trade name Oragallin 8 for Osterreichische Stickstoffwerke, AG, Linz/Donau - Austria. 2-2. Formula and Molecular Weight CI [CioHi4ClN30S (259.77)] 4 EZZAT M. ABDEL-MOETY AND HAMAD A. AL-KHAMEES 2-3. The Chemical Abstract Registry (CAS) Number: [ 1830-32-61- 2-4 . Appearance. Color, Odor, and Taste Microcrystalline, white, odorless powder with bitter taste. 2-5. Physical Characteristics 2-51. Melting Range The melting of azintamide was carried out at a heating rate of 1"C.min-1 on a Kofler hot-stage microscope. Table 1: Melting point and range of azintamide* Start temperature Melting range Mid-point Literature ( ' C ) ( " C ) ( " C ) t 'C) 90 95.0-97.0 96.0 98-100 (2.0) ( 2 ) 95.5-97.5 96.5 97-98 (2.0, ( ~ 3 ) *Sample from Bsterreichishe Stickstoffwerke, AG, Linz/Donau- Austria, BN: 23540/524699 - all values ( ' C ) are uncorrected. 2-52. Differentional Thermal Scanning (DSC) The DSC-curve was obtained on a DuPont TA- 9900 Thermal Analyzer attached to a data processing unit. Figure 1 shows the DSC-curve of azintamide. The running was between 50-150°C at heating rate of 10"C.min-1. The heat of activation and the purity of the sample was determined using purity program. 2-53. Solubility Azintamide is freely soluble in benzene, chloroform, ethyl acetate and acetone, its solubility in water is 5 mg.ml-1 (1).
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