BELT Ce LC HPLC Methods for Drug AnalysisStability-Indicating HPLC Methods for Drug Analysis Quanyun A. Xu, PhD Research Scientist, Clinical Pharmaceutics Research Program Division of Pharmacy University of Texas M.D. Anderson Cancer Center Houston, Texas Lawrence A. Trissel, FASHP Director, Clinical Pharmaceutics Research Program Division of Pharmacy University of Texas M.D. Anderson Cancer Center Houston, Texas American Pharmaceutical Association ‘Washington, D.C. APhA (PP Pharmaceutical Press h London, EnglandAcquiring Editor: Julian I Gravbart Copyeditor: L. Luan Corrigan Layout and Graphies: Claire Purell Cover Design: Jonathan Pennell Proofreader: Nancy Lorince © 1999 by Quanyun A. Xu and Lawrence A. Trissel Published by the American Pharmaceutical Association 2215 Constitution Avenue, N.W. ‘Washington, DC 20037-2985 www.aphanetorg and the Pharmaceutical Press 1 Lambeth High Street London SEI TIN, United Kingdom \worw.pharmpress.com All ights reserved [No part ofthis book may be reproduced, stored in a retrieval system, or transmitted in any form ‘or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written ‘permission from the publisher Library of Congress Cataloging-in-Publication Data Xu, Quanyun A., 1961- Stability-indicating HPLC methods for drug analysivQuanyun A. Xu, Lawrence A. Tisel, pom. Includes bibliographical references and index. ISBN 0-917330-95-1 (hardbound) 1. Druge-Analysis. 2. High performance liquid chromatography. 3. Drug stability. 1. Trissel, Lawrence A, [DNLM: 1. Chromatography, High Pressure Liguid~methods. 2. Drug Stability. 3. Pharmaceutical Proparations-analysis. QV 25 X8s 1999] RSI89.5,HS4X8_ 1999 61571901421 DNLMIDLC for Library of Congress 99-20308 cP. ISBN in the UK: 0-85369-448-6This book is dedicated to those who recognize the benefits to patient care that flow from applied pharmaceutical science. To Honggin, Michael, and Andy for love and joy in life QAX To Cyndi, our hope and pride, To Karl, a friend and mentor who is greatly missed, And to Pam, for everything you do LATCONTENTS Foreword ix Preface xi Using This Book xiii Monographs 1 Index 383Foreword iquid chromatography is widely [Lo eiceettesin ey of mates Improvement in oth ihe sensi of deicas andthe pesto ance of clunas have made ita method of Ghote forthe analysis drags, Numerous Spolaton have been pushed and the iterates replete wth nalyteal methods deserting the chomaiogaphic metbods fora wide ange of sal leu. Many tes tre eval which simmarns these inethods. However, while these ens capi avast munber of pubisied papers thy often reduce the method ta sige tine of information, which describes the chromatographic condition sed Furthermore th Sabian ability ofthese methods snot inated andi fat few ae sbiy ndesting maths This is thesoengin of is bok isthe fintcomplaton of sbi indaing met Od. Each of he 250 monopaps provides Sumas of meh which ae kao to be subg indcing. AS sch forse ined in evaiating dug sbi, this boak oil ily become valuable esure 2 nk of fitter. ew mes tiga can apily demise i sabi indcaing method ha ever een dele ands te speis of he mend and te tne which dopaon prota’ wee Gbained are ity esrb Even for companies and busin with vast mouse or iad wih Sesitop trae searching. capably, this bok can save precious tie. While would be common o complete Hrase trac, tbe tne ried trae ad Grate each published metod for iss bliyndeating ality is evs and ean beside by fat reviewing is book. Furthermore, this text does more than provide a brief one-line summary of the avail- able methods. Each of the 250 monographs {argets 27 unique elements of each published ‘method in a structured format. This format summarizes important chemical information and provides a summary of the previously published method. The summary of this sec- tion is sufficiently detailed to allow analysts ‘with chromatographic experience to set up @ ‘method and begin the process of validation. The process of validating the method within their own laboratory is also aided by this work because the procedure by which the authors ‘demonstrated that the method was stability indicating is also delineated. Asis often the case, texts ofthis type are limited by the original published work. Ifthe ‘original work was edited or the authors did not include some information in their paper, a summary will obviously be missing the infor. ‘mation. ‘This book is no different from other works that summarize information from pub- lished articles. It includes monographs in which some information does not appear because the information was not available in the original articles. Nevertheless, Xu and Trissel have created a valuable time-saving. tool for those of us who are involved in assessing the stability of pharmaceuticals. It is the first of its kind, and this book will undoubtedly become a valuable resource in any laboratory dealing with drug stability. Scott E, Walker, MScPhm Coordinator, Research and Quality Control Department of Pharmacy ‘Sunnybrook Health Science Centre North York, Ontario Associate Professor, University of Toronto February 1999Preface tability Indicating HPLC Methods AY ‘of summaries of stabilty-indicating high-performance liquid chromatographic (HPLC) analytical methods that have appeared in the published literature. The information is presented as. structured monographs on 250 diferent drug entities. “The work is unique in focusing only on sta: bility-indicating HPLC methods, a special- ized subset of all HPLC methodologies that are useful to those involved with eval- uating drug stability, dosage form develop- ment, quality control, and drug regulation The intial steps an analyst must take ‘when beginning the process of analyzing ‘an unfamiliar drug inevitably have included «8 search for previously published analytical ‘methods for that drug. Often, this takes the form of a computer search of the published literature. Usually being very general in nature, these searches often list a multipic- ity of methods that are not relevant to the specific kind of application the analyst has in mind. This can lead to much tedious library time collecting and evaluating articles tha, in the end, may or may not be useful Other compilations of analytical meth- ods have tended to be general in nature as well, encompassing methods for a variety of applications. Because so much of the Published literature describing analytical techniques is focused on determinations of drug concentrations in biological matrices, stability-indicating methods tend to be given less attention or even left out alto- gether, For those analysts whose work involves the determination of the stability of pharmaceutical dosage forms, most published analytical methodologies have not been demonstrated to be suitable. Consequently, many methods will be of uncertain applicability at best when obtained from computer searches or pub- lished compilations. Ithas always seemed to us that the best starting point in identifying a suitable sta bility-indicating analytical method is from methods previously shown to be stability indicating in studies by other researchers. OF course, finding an analytical method in the literature that was found to be stability indicating in a previous study does not ‘mean that the method need not be evaluat- ed in the analyst’s hands. The analyst is still obligated to assure the adequacy of the method for specificity, precision, repro- bumetanide occurred after treatment with base. Standard curves for bumetanide were constructed from 0.015 to 0.025 mg/mL. and from 0.15 to 0.3 mg/mL. Correlation coefficients were 0.998. The intraday and inter- day coefficients of variation were less than 2.6% Reference Cornish LA, Montgomery PA, Johnson CE. Stability of bumetanide in 5% dextrose injec- tions. Am J Health Syst Pharm. 1997; 54: 422-23. Bupivacaine Chemical Names I-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide; di-|-butyl-2’,6-pipecoloxylidide Other Names Mareaine, Sensorcaine Form Molecular Formula Molecular Weight Bupivacaine CHO 2884 Bupivacaine hydrochloride CyyHaCIN,O 3249 Appearance Bupivacaine hydrochloride is white, odorless erystalline powder. Solubility Bupivacaine hydrochloride is frely soluble in water and alcohol. vk, Bupivacaine hydrochloride has a pK, of 8.1 Method 1 Grassby and Roberts investigated the stability of epidural opiate solutions in 0.9% sodi- um chloride infusion bags using an HPLC method. The chromatographic system consist- ed of a Kratos SF 400 pump, Philips PU4700 204uL. loop injector, and a Uvikon 740LC UV detector. The stationary phase was a Chrompak Spherisorb ODS-2 column (250 x 4.6