HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF (SR)-ENANTIOMERS AND (RS)-ENANTIOMERS OF MEFLOQUINE IN PLASMA AND CAPILLARY BLOOD SAMPLED ON PAPER AFTER DERIVATIZATION WITH (-)-1-(9-FLUORENYL)ETHYL CHLOROFORMATE

A sensitive, stereoselective and rapid reversed-phase liquid chromatog raphic method for the determination of (SR)- and (RS)-mefloquine enant iomers in 100 mul plasma and capillary blood collected on chromatograp hic paper is presented. The assay involves protein precipitation from plasma, liquid-liquid extraction of mefloquine from plasma, capillary blood with methyl tert.-butyl ether under alkaline conditions and deri vatization of MQ with (-)-1-(9-fluorenyl)ethyl chloroformate. Liquid c hromatographic separation of the diastereomers was performed using an C18 reversed-phase column with acetonitrile-water-acetic acid 82:18:0. 07 (v/v/v) as the mobile phase, and a flow-rate of 1.0 ml/min. When us ing 100 mul of plasma the limit of, determination is 250 nmol/l with u ltraviolet- and 10 nmol/l with fluorescence detection. The present met hod offers several advantages over those previously reported; very low limit of determination, small sample volume, sampling onto paper and use of an inexpensive standard achiral HPLC column. No racemization du ring the derivatization procedure or storage of the MQ enantiomers was found.