ENANTIOSELECTIVE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF (SR)-MEFLOQUINE AND (RS)-MEFLOQUINE IN PLASMA USING N-BENZYLOXYCARBONYL-GLYCYL-L-PROLINE AS CHIRAL COUNTER ION

A stereoselective HPLC method is described for the determination of (S R)-and (RS)-mefloquine in plasma. The direct chiral separation is carr ied out on a Hypercarb-S column (porous graphitised carbon) with N-ben zyloxycarbonyl-glycyl-L-proline (L-ZGP) as a chiral counter-ion in a r eversed-phase system. The sample work-up included protein precipitatio n by addition of zinc sulphate and acetonitrile followed by liquid-liq uid extraction with methyl-tert.-butyl ether. After evaporation of the organic phase, the residue is dissolved in the mobile phase and injec ted onto the column. Analyses of the enantiomers in plasma after a sin gle oral dose of mefloquine indicates that the pharmacokinetics of the two enantiomers are different. The method is validated by determining the absolute recovery, linearity, accuracy, precision and inter- and intra-assay variation.