Achiral and chiral HPLC analysis of norverapamil and its metabolites in microsomal samples

Achiral and chiral HPLC (high performance liquid chromatography) were devel oped for monitoring norverapamil and its two metabolites in in vitro micros omal samples. Norverapamil is a chiral drug with the same ability as verapa mil in reversing MDR (multi-drug resistance) against some cytostatics. R(+) norverapamil is less cardiotoxic as S(-) enantiomer and so it could be app lied in higher concentrations. HPLC conditions were worked out for both achiral and chiral assays and very simple and effective preseparation procedure (SPE - solid phase extraction ) was used for microsomal sample as clean-up step before HPLC analysis. The total concentrations of norverapamil and its metabolites were calculate d from achiral chromatograms and the ratio of enantiomers were determined f rom chiral separations. The complete assay could be used for both in vitro and in vivo experiments.