Enantioselective quantification of chiral drugs in human plasma with LC-MS/MS

Today, approximately 60% of synthetic drugs are chiral and 88% of these chiral synthetic drugs are used therapeutically as racemates. However, for many racemic drugs, their stereospecific plasma pharmacokinetics in humans are not known due to the limitations of the analytical methods. Nowadays, liquid chromatography (LC)-tandem mass spectrometry (MS/MS) methods based on various chiral stationary phases (CSPs), with a high degree of specificity and sensitivity, have been widely used in enantioselective determination of chiral drugs and/or their metabolites in human plasma. The technologies and issues when coupling chiral chromatography with MS/MS detection in bioanalytical methods will be reviewed herein. The introduction and applications of various CPSs, including polysaccharide-, macrocyclic glycopeptide-, protein- and cyclodextrin-based phases, are described here. This review also includes a discussion of interface and matrix effects in enantioselective LC-MS/MS methods.