Bioactivity and analysis of chiral compounds

Abstract

The stereochemistry of drug and xenobiotic metabolism and toxicokinetics have recently become an issue for the pharmaceutical industry and the regulatory authorities. Chirality is an intrinsic property of macromolecular structures in the cells such as enzymes, receptors, and nucleic acids which becomes evident when they interact with a chiral drug or xenobiotic molecule, showing a high degree of stereoselectivity. There are now a range of examples of isomeric compounds whose biological activity may well reside predominantly in one enantiomer. The differences in the biological activities between enantiomers have resulted in an increased interest in determination of enantiomeric composition of drugs, xenobiotics, and/or their metabolites. The difficulty in determining enantiomeric excess arises from the fact that enantiomers have identical physicochemical properties in a non-chiral environment. The major analytical breakthrough has come with the emergency of commercially available chiral stationary phases for capillary gas chromatography, high-performance liquid chromatography, and capillary electrophoresis.