Enantioselective high-performance liquid chromatographic determination of (SR)- 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 (SR)- and (RS)-mefloquine in plasma. The direct chiral separation is carried out on a Hypercarb-S column (porous graphitised carbon) with N-benzyloxycarbonyl-glycyl-L-proline (L-ZGP) as a chiral counter-ion in a reversed-phase system. The sample work-up included protein precipitation by addition of zinc sulphate and acetonitrile followed by liquid-liquid extraction with methyl-tert.-butyl ether. After evaporation of the organic phase, the residue is dissolved in the mobile phase and injected onto the column. Analyses of the enantiomers in plasma after a single 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.