DETERMINATION OF S-12024 ENANTIOMERS IN HUMAN PLASMA BY LIQUID-CHROMATOGRAPHY AFTER CHIRAL PRECOLUMN DERIVATIZATION

S 12024-2 is a new drug in phase II development that possesses cogniti ve enhancing properties. As its molecular structure has a chiral centr e, a stereoselective method for the analysis of both enantiomers in hu man plasma has been developed. The method involves pre-column derivati zation of the amine moiety with a homochiral reagent (+)-1-(9-fluoreny l)ethyl chloroformate (FLEC), and chromatographic separation of the tw o diastereoisomers on an achiral reversed-phase cyanopropyl column, wi th fluorimetric detection (lambda(ex) = 260 nm; lambda(em) = 310 nm). A liquid-liquid extraction procedure with diethyl ether-dichloromethan e (70:30, v/v) was used for sample preparation. This technique provide s a linear response for both enantiomers over a concentration range of 10-500 ng ml(-1) and the quantitation limit was set at 5 ng ml(-1) in human plasma. Within-day and between-day precision and accuracy are w ithin 9% limits for all concentrations assessed. This procedure was th erefore used for determining both enantiomers in human plasma followin g oral administration of racemic S 12024-2 to elderly healthy subjects .