ABSTRACT

The study of xenobiotic metabolism is a key feature for the pharmaceutical and chemical industries since it is a determining factor both in the preclinical development of new drugs and in the toxicity evaluation of chemicals. For enzymatic studies, capillary electrophoresis (CE) has been classically employed only as separation system after offline reactions. To evaluate the enantioselective metabolism of racemic compounds, it is necessary to integrate methodologies that allow, first, the interaction of racemic xenobiotics with the enzymatic system and later the determination of the enantiomers of intact xenobiotic or its metabolites in the reaction mixture. Ketamine is a chiral phencyclidine derivative, which is used as an anesthetic drug and postoperative analgesic. The combination of electrophoretically mediated microanalysis for the in-line development of an enzymatic assay and "partial filling technique" (PFT) with a cyclodextrin for the chiral separation of substrates and/or metabolites has proved to be a powerful tool for a fast evaluation of in vitro enantioselective metabolism of drugs.