STUDIES OF THE METABOLISM OF THE ANTIHISTAMINIC DRUG DIMETHINDENE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND CAPILLARY ELECTROPHORESIS INCLUDING ENANTIOSELECTIVE ASPECTS

A reversed-phase high-performance liquid chromatography method for the determination of dimethindene and its main metabolites N-demethyldime thindene, 6-hydroxydimethindene and 6-hydroxy-N-demethyldimethindene i n human urine was developed. The assay was also applied to the quantif ication of dimethindene-N-oxide in rat urine. Conjugates of the hydrox ylated metabolites were determined after enzymatic deconjugation. More over the direct determination of dimethindene and its metabolites with out prior extraction from urine was performed by capillary electrophor esis. The direct simultaneous determination of the enantiomers of dime thindene and N-demethyldimethindene was achieved on a Chiralcel OD col umn. Urinary data after oral administration of dimethindene are presen ted. The assays were used to study dimethindene and it metabolites in urine upon oral administration of the drug to rats and human volunteer s.