INVESTIGATION OF THE STEREOSELECTIVE METABOLISM OF PRAZIQUANTEL AFTERINCUBATION WITH RAT-LIVER MICROSOMES BY CAPILLARY ELECTROPHORESIS ANDLIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY

Two different separation methods for the antischistosomal drug praziqu antel and its metabolites by capillary electrophoresis are described. Achiral separation was obtained by micellar electrokinetic capillary c hromatography using sodium dodecyl sulfate as micelle-forming surfacta nt. On the other hand, the negatively charged sulfobutylether-beta-cyc lodextrin as a chiral selector enabled the separation of the drug and its metabolites as well as their enantioseparation. Based on this sepa ration, the enantioselectivity of the metabolism of praziquantel was s tudied by incubation of the drug with rat liver microsomes. Whereas tr ans-and cis-4-hydroxypraziquantel were mainly formed from the R-(-)-en antiomer, another, different monohydroxylated metabolite was only form ed from the S-(+)-enantiomer. Information about the structure of these metabolites was obtained, using LC-MS. (C) 1998 Elsevier Science B.V.