Enantioselective analytical methods in pharmacokinetics with specific reference to genetic polymorphic metabolism

The new trend towards developing enantiospecific drugs has increased the interest in enantiospecific pharmacokinetics of chiral drugs, mainly in the case where only one of the two enantiomers is responsible for the pharmacological activity. Enantiospecific bioassays are also useful in investigating the pharmacokinetic behaviour of the two enantiomers when a given drug is marketed as racemate. The stability of the stereogenic centre in vitro and in vivo, as far as unidirectional and bidirectional inversions are concerned, is another reason for requiring stereospecific assay and bioassay. These assays are often complicated in order to achieve quantification, mainly for in vivo measurements, which are often in the low pg/ml range. This paper considers the enantiospecific bioassays, the methods and approaches used, the need for chemical derivatization, and the difficulties involved. It includes a specific discussion for the genetic polymorphic metabolism involving stereogenic centres. (C) 2002 Published by Elsevier Science B.V.