高效液相色谱验证-英文.pdf

3 METHOD VALIDATION FOR HPLC ANALYSIS OF RELATED SUBSTANCES IN PHARMACEUTICAL DRUG PRODUCTS Y. C. LEE, PH .D. Patheon YM, Inc. 3.1 INTRODUCTION In this chapter we outline the general requirements for analytical method valida- tion for HPLC analysis of related substances in pharmaceutical products. Most of the discussion is based on method validation for pharmaceutical products of synthetic origin. Even though most of the requirements are similar for other types of pharmaceutical drug products (e.g., biopharmaceutical drug products), detailed discussion of method validation for other types of pharmaceutical drug products is outside the scope of this chapter. The discussion focuses on current regulatory requirements in the pharmaceutical industry. Since the expectations for method validation are different at different stages of the product development process, the information given in this chapter is most suitable for final method valida- tion according to the ICH requirements to prepare for regulatory submissions (e.g., NDA). Even though the method validation is related to HPLC analysis, most of the principles are also applicable to other analytical techniques (e.g., TLC, UV). Analytical Method Validation and Instrument Performance Verification, Edited by Chung Chow Chan, Herman Lam, Y. C. Lee, and Xue-Ming Zhang ISBN 0-471-25953-5 Copyright  2004 John Wiley Sons, Inc. 27 28 METHOD VALIDATION FOR HPLC ANALYSIS OF RELATED SUBSTANCES 3.2 BACKGROUND INFORMATION 3.2.1 Definitions Definitions for some of the commonly used terms in this chapter are given below. ž Drug substance (active pharmaceutical ingredient): a pharmaceutical active ingredient. ž Related substances: impurities derived from the drug substance and there- fore not includin