Mass Spectrometry In Drug Discovery

This Page Intentionally Left Blank ISBN: 0-8247-0607-2 This book is printed on acid-free paper. Headquarters Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016 tel: 212-696-9000; fax: 212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 812, CH-4001 Basel, Switzerland tel: 41-61-261-8482; fax: 41-61-261-8896 World Wide Web http:/ /www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright  2002 by Marcel Dekker, Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA Preface The recent, pervasive use of liquid chromatography/mass spectrometry (LC/MS) is providing sensitive, selective, rapid, and information-rich analytical methodology to drug discovery research. With the possible exception of combinatorial chemistry, no single technology has revolutionized and streamlined the drug discovery process to such a great extent. In the hopes of expediting the drug discovery process, major pharmaceutical companies have invested considerable financial and human resources in mass spectrometers. Current pharmaceutical development has become more demanding, especially with the advent of high-throughput discovery programs across the industry in the areas of chemistry, pharmacology, and pharmacokinetics. In this regard, interdisciplinary rapid-screening protocols that allow for the examination of an increased number of new chemical entities (NCEs) have arisen. Many of these new screening protocols have been successful due in large part to the ability of the mass spectrometer to function as a sensitive and selective detector with minimal method development effort. Drug discovery has been the subject of many articles in peer-reviewed journals, but until now no concise treatise had been written to bring together the numerous applications of mass spectrometry and drug discovery. Mass Spectrometry in Drug Discovery is intended to bring the knowledge gap that the widespread use of LC/MS has created. From a practical and applied point of view, the text will introduce readers to the basic concepts of mass spectrometry and atmospheric pressure ionization LC/MS. Although many aspects of mass spectrometry are encompassed, the book focuses more on applications associated with pharmaceutics, pharmacokinetics, and combinatorial chemistry; iii iv Preface it is not intended to incorporate the abundance of applications in the areas of pharmacology and toxicology. Nor is this book intended just for those in drug metabolism who have extensive experience in mass spectrometry. Rather, it is hoped that any scientist interested in applying LC/MS to drug discovery will benefit, including those who may not have received any prior training in the area. Moreover, this book should serve as a background text for those wh