54511_C000.fm Page i Tuesday, September 4, 2007 10:49 AM Half Title Page Postmortem Toxicology of Abused Drugs 54511_C000.fm Page ii Tuesday, September 4, 2007 10:49 AM 54511_C000.fm Page iii Tuesday, September 4, 2007 10:49 AM Title Page Postmortem Toxicology of Abused Drugs Edited by Steven B. Karch, MD, FFFLM Consultant Pathologist and Toxicologist Berkeley, California Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business 54511_C000.fm Page iv Tuesday, September 4, 2007 10:49 AM CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2008 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-13: 978-1-4200-5451-4 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or uti- lized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopy- ing, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http:// www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For orga- nizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Postmortem toxicology of abused drugs / [edited by] Steven B. Karch. p. ; cm. “A CRC title.” Includes bibliographical references and index. ISBN-13: 978-1-4200-5451-4 (alk. paper) ISBN-10: 1-4200-5451-1 (alk. paper) 1. Forensic toxicology. 2. Drugs of abuse--Toxicology. 3. Autopsy. I. Karch, Steven B. [DNLM: 1. Autopsy--methods. 2. Forensic Toxicology--methods. 3. Street Drugs--poisoning. W 825 P858 2007] RA1228.P67 2007 614’.13--dc22 2007008111 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com 54511_C000.fm Page v Tuesday, September 4, 2007 10:49 AM Contents Chapter 1 Introduction to Postmortem Toxicology....................................................................1 W. Lee Hearn, Ph.D. and H. Chip Walls, B.S. Chapter 2 Specimen Selection, Collection, Preservation, and Security..................................13 Bradford R. Hepler, Ph.D. and Daniel S. Isenschmid, Ph.D. Chapter 3 Common Methods in Postmortem Toxicology........................................................31 W. Lee Hearn, Ph.D. and H. Chip Walls, B.S. Chapter 4 Strategies for Postmortem Toxicology Investigation...............................................67 Edited and Revised by Henrik Druid, M.D., Ph.D. Chapter 5 Quality Assurance in Postmortem Toxicology........................................................95 Wilmo Andollo, B.S. Chapter 6 Interpretation of Postmortem Drug Levels............................................................113 Graham R. Jones, Ph.D., DABFT Appendix I Glossary of Terms in Forensic Toxicology...........................................................131 Compiled by H. Chip Walls, B.S. Appendix II Common Abbreviations........................................................................................137 Compiled by H. Chip Walls, B.S. Appendix III References for Methods of Drug Quantitative Analysis.....................................141 Appendix IV Sample Calculations............................................................................................181 Barry K. Logan, Ph.D. and Alan Wayne Jones, D.Sc. Appendix V Predicted Normal Heart Weight (g) as a Function of Body Height in 392 Women and 373 Men......................................................................................185 Index..............................................................................................................................................187 54511_C000.fm Page vi Tuesday, September 4, 2007 10:49 AM 54511_C000.fm Page vii Tuesday, September 4, 2007 10:49 AM Preface Because of the continuous increase in availability and use of pharmaceuticals and illicit drugs, postmortem toxicology has become more and more important in death investigations. The intro- duction of new substances to the market requires a high awareness among pathologists and toxi- cologists and necessitates the development of methods that encompass the newcomers. Fortunately, many important achievements have been made in methodology, and the application of novel techniques, such as modifications of solid phase extraction and LC/MS techniques, now offers better conditions for efficient and sensitive analyses of numerous substances. Many important contributions regarding the impact of various postmortem changes that may influence the toxicological results have been published. Pharmacogenetic analyses, e.g., to identify poor metabolizers, may now be applied on postmortem material and assist in the determination of the manner of death, and studies on postmortem redistribution of drugs have resulted in a widespread appreciation of the influence of the specimen type on the drug concentrations. In recent years, the specific detection of many compounds and their metabolites in various matrices has improved substantially. However, the interpretation of their concentrations remains a difficult task. Hence, despite the progress in postmortem toxicology, information about previous drug use and the circumstances surrounding death, and the autopsy findings are still very important in order to arrive at correct conclusions when interpreting the analytical results. An intimate collaboration between toxicologists and pathologists is therefore desirable. Traditionally, teachers of forensic science have always emphasized that the proper investigation of a drug-related death involves three elements: scene investigation, autopsy, and toxicological examination. The traditional approach is no longer valid because it assumes that the autopsy was complete. We now know that it has never been complete. Heart disease is not ruled out just because 25 sections of myocardium look normal. Poisoning is not proven just because blood morphine concentrations are very high. We now live in the age of the DNA microarray. Chips for measurement of CYP2D6 polymorphisms are already available commercially. Arrays for the measurement of the hundreds of genes involved in hypertrophic cardiomyopathy already exist in development labs. The sooner these new technologies are incorporated into forensic toxicology, the sooner the justice system will benefit. 54511_C000.fm Page viii Tuesday, September 4, 2007 10:49 AM 54511_C000.fm Page ix Tuesday, September 4, 2007 10:49 AM The Editor Steven B. Karch, M.D., FFFLM, received his under- graduate degree from Brown University. He attended grad- uate school in anatomy and cell biology at Stanford Univer- sity. He received his medical degree from Tulane University School of Medicine. Dr. Karch did postgraduate training in neuropathology at the Royal London Hospital and in cardiac pathology at Stanford University. For many years he was a consultant cardiac pathologist to San Francisco’s Chief Medical Examiner. In the U.K., Dr. Karch served as a consultant to the Crown and helped prepare the cases against serial murderer Dr. Harold Shipman, who was subsequently convicted of murdering 248 of his patients. He has testified on drug abuse–related matters in courts around the world. He has a special interest in cases of alleged euthanasia, and in episodes where mothers are accused of murdering their children by the transference of drugs, either in utero or by breastfeeding. Dr. Karch is the author of nearly 100 papers and book chapters, most of which are concerned with the effects of drug abuse on the heart. He has published seven books. He is currently completing the fourth edition of Pathology of Drug Abuse, a widely used textbook. He is also working on a popular history of Napoleon and his doctors. Dr. Karch is forensic science editor for Humana Press, and he serves on the editorial boards of the Journal of Cardiovascular Toxicology, the Journal of Clinical Forensic Medicine (London), Forensic Science, Medicine and Pathology, and Clarke’s Analysis of Drugs and Poisons. Dr. Karch was elected a fellow of the Faculty of Legal and Forensic Medicine, Royal College of Physicians (London) in 2006. He is also a fellow of the American Academy of Forensic Sciences, the Society of Forensic Toxicologists (SOFT), the National Association of Medical Examiners (NAME), the Royal Society of Medicine in London, and the Forensic Science Society of the U.K. He is a member of The International Association of Forensic Toxicologists (TIAFT).