or pharmaceutical and biotechnological products (ahujachiral separation methods) high-throughput screening and method development strategies to separate chiral drug compounds in hplc, sfc, 英文精品课件.pdf

CHAPTER 12 High-Throughput Screening and Method Development Strategies to Separate Chiral Drug Compounds in HPLC, SFC, and CE HASRET ATES, DEBBY MANGELINGS, and YVAN VANDER HEYDEN Department of Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel–VUB, Brussels, Belgium 1 INTRODUCTION Chirality is a molecular phenomenon that has a significant impact in a phar- maceutical context. A chiral molecule is defined as a compound that is not superimposable on the molecule that forms its mirror image [1]. This can be caused by the presence of a chiral center, a chiral plane, a chiral axis, or a heli- cal structure in the molecule [1,2]. Such a chiral compound and its mirror image form a pair of enantiomers. Enantiomers have the same chemical and physical properties when they are put in an achiral environment. When the enantiomers are put in a chiral environment, such as the human body, they behave as two dif- ferent compounds. In pharmaceutical applications this can lead to very hazardous consequences. When a chiral drug molecule is administered as a racemate, it is possible that only one enantiomer is therapeutically active. This enantiomer is called the eutomer . The other enantiomer, the distomer , can react with the same target, showing less effect, or it may not react at all. But it is also possible that the therapeutically less active or inactive enantiomer can cause effects opposite to those of the eutomer, or its effect can even be toxic. In fact, it can be stated that the eutomer and distomer differ in their pharmacological, pharmacodynamic, pharmacokinetic and toxicological properties. Chiral Separation Methods for Pharmaceutical and Biotechnological Products, Edited by Satinder Ahuja Copyright © 2011 John Wiley Sons, Inc. 383 3