Mass Spectrometry In Medicinal Chemistry: Applications In Drug Discovery (methods And Principles In Medicinal Chemistry)

Mass Spectrometry in Medicinal Chemistry Edited by Klaus T. Wanner and Georg Ho¨fner Mass Spectrometry in Medicinal Chemistry Edited by Klaus T. Wanner and Georg Ho¨fner Mass Spectrometry in Medicinal Chemistry Edited by Klaus T. Wanner and Georg Ho¨fner Series Editors Prof. Dr. Raimund Mannhold Molecular Drug Research Group Heinrich-Heine-Universita¨t Universita¨tsstrasse 1 40225 Du¨sseldorf Germany [email protected] Prof. Dr. Hugo Kubinyi Donnersbergerstrasse 9 67256 Weisenheim am Sand Germany [email protected] Prof. Dr. Gerd Folkers Collegium Helveticum STW/ETH Zurich 8092 Zurich Switzerland [email protected] 9 All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. Library of Congress Card No.: applied for British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Bibliographic information published by the Deutsche Nationalbibliothek Die Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available in the Internet at hhttp://dnb.d-nb.dei. 8 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Volume Editors Prof. Dr. Klaus T. Wanner Ludwig-Maximilians-University Munich Department of Pharmacy Center of Drug Research Butenandtstr. 7 81377 Munich Germany [email protected] Dr. Georg Ho¨fner Ludwig-Maximilians-University Munich Department of Pharmacy Center of Drug Research Butenandtstr. 7 81377 Munich Germany [email protected] All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law. Printed in the Federal Republic of Germany Printed on acid-free paper Typesetting Asco Typesetter, Hong Kong Printing betz-druck GmbH, Darmstadt Binding Litges & Dopf GmbH, Heppenheim Cover Design Grafik-Design Schulz, Fußgo¨nheim Wiley Bicentennial Logo Richard J. Pacifico ISBN 978-3-527-31456-0 V Contents Preface XV A Personal Foreword List of Contributors XVII XIX 1 I Introduction to MS in bioanalysis 1 Mass Spectrometry in Bioanalysis – Methods, Principles and Instrumentation 3 Ge´rard Hopfgartner 1.1 1.2 1.3 1.3.1 1.3.2 1.3.2.1 1.3.2.2 1.3.2.3 1.3.2.4 1.3.2.5 1.3.3 1.4 1.4.1 1.4.2 1.4.3 1.4.4 1.4.5 1.4.6 1.4.6.1 1.4.6.2 1.5 1.6 Introduction 3 Fundamentals 4 Ionization Techniques 10 Electron Impact and Chemical Ionization 10 Atmospheric Pressure Ionization 12 Electrospray 14 Atmospheric Pressure Chemical Ionization 17 Photoionization 19 Multiple Ionization S