Handbook Of Modern Pharmaceutical Analysis

HANDBOOK OF MODERN PHARMACEUTICAL ANALYSIS This Is Volume III of SEPARATION SCIENCE AND TECHNOLOGY A reference series edited by Satinder Ahuja HANDBOOK OF MODERN PHARMACEUTICAL ANALYSIS Edited by Satinder Ahuja Ahuja Consulting Calabash, North Carolina Stephen Scypinski RW Johnson Pharmaceutical Research Institute Raritan, New Jersey San Diego San Francisco New York Boston London Sydney Tokyo This book is printed on acid-free paper. Copyright © 2001 by Academic Press 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. The appearance of the code at the bottom of the first page of a chapter in this book indicates the Publisher’s consent that copies of the chapter may be made for personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per-copy fee through the Copyright Clearance Center, Inc. (222 Rosewood Drive, Danvers, Massachusetts 01923), for copying beyond that permitted by Sections 107 or 108 of the U.S. Copyright Law. This consent does not extend to other kinds of copying, such as copying for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. Copy fees for pre-2001 chapters are as shown on the title pages; if no fee code appears on the title page, the copy fee is the same as for current chapters. 01 $35.00. The information provided in this handbook is compiled from reliable sources but the authors, editor, and the publisher cannot assume any responsibility whatsoever for the validity of all statements, illustrations, data, procedures, and other related materials contained herein or for the consequence of their use. ACADEMIC PRESS A Harcourt Science and Technology Company 525 B Street, Suite 1900, San Diego, CA 92101-4495, USA http://www.academicpress.com Academic Press Harcourt Place, 32 Jamestown Road, London, NW1 7BY, UK Library of Congress Catalog Number: 2001088201 International Standard Book Number: 0-12-045555-2 Printed in the United States of America 00 01 02 03 HP 9 8 7 6 5 4 3 2 1 CONTENTS CONTRIBUTORS xiii PREFACE xvii 1 Modern Pharmaceutical Analysis: An Overview SATINDER AHUJA I. II. III. IV. V. VI. VII. 2 Identity and Purity Requirements 2 Bioavailability/Dissolution Requirements 4 Regulatory Considerations 5 Regulatory Compliance 8 International Conference on Harmonization 9 Global CMC NDA 9 Highlights of Modern Pharmaceutical Analysis 10 References 22 Combinatorial Chemistry and High-Throughput Screening in Drug Discovery and Development KEN APPELL, JOHN J. BALDWIN, AND WILLIAM J. EGAN I. Introduction 24 II. Combinatorial Methods 25 v vi CONTENTS III. IV. V. VI. VII. VIII. IX. X. XI. XII. XIII. XIV. Methods for Structural Assignment 26 Diversity 28 Druglikeness 28 Designing Combinatorial Libraries with Optimal ADME Properties 28 Existing Computational Methods for ADME Properties 30 Optimization Philosophy 35 Applying Existing ADME Models to Combinatorial Library Design 37 The Future of ADME Modeling 38 High-Throughput Screening and Combinatorial Chemistry 39 Assay Plate Formats: Move to Miniaturization 40 Nonseparation or Homogeneous Assays 43 Identification of Receptor Antagonists for Chemokine Receptor and Bradykinin-1 by Screening a 150,000-Member Combinatorial Library 44 XV. Structure-based Design of Somatostatin Agonists 47 XVI. Conclusions 48 References 49 3 Solid-State Analysis HARRY G. BRITTAIN I. II. III. IV. V. 4 Introduction 57 Pr