chiral separation methods for pharmaceutical and biotechnological products (ahujachiral separation methods) basic considerations in hplc method development of chiral compounds英文精品课件.pdf

CHAPTER 3 Basic Considerations in HPLC Method Development of Chiral Compounds SATINDER AHUJA Ahuja Consulting, Calabash, North Carolina 1 INTRODUCTION Chiral molecules (from the Greek word cheiro , meaning “hand”) relate to each other as an object and its mirror image that are not superimposable (i.e., they are like a pair of hands). These molecules, also called enantiomers , can have significant differences in biological activity. The differences in pharmacologi- cal, metabolic, or toxicologic activity relate to the arrangements of atoms in a molecule (i.e., its stereochemistry). This explains why regulatory requirements in the pharmaceutical industry demand detailed investigations of chiral molecules [1,2]. Small molecules are covered in this chapter; large biomolecules are dis- cussed in Chapter 15. The reader may find of some interest earlier publications and presentations that deal at length with this subject [1–3]. Before initiating method development, it is desirable to develop a basic knowledge of stereochemistry [1–7]. Some basic information on stereochemistry is provided in Section 2.1 to help the reader develop a better understanding of the separation mechanisms that come into play in various separation methods used for chiral compounds. This knowledge will help the reader select a suitable chiral separation method, based on the molecular structure of the chiral compound of interest. Logical reasons for the selection process are discussed later in the chapter. Chiral Separation Methods for Pharmaceutical and Biotechnological Products, Edited by Satinder Ahuja Copyright © 2011 John Wiley Sons, Inc. 35 36 BASIC CONSIDERATIONS IN HPLC METHOD DEVELOPMENT OF CHIRAL COMPOUNDS 2 DETERMINING THE CHIRALITY OF A MOLECULE Look at the st