DETERMINATION OF THE STEREOCHEMICAL COMPOSITION OF THE MAJOR METABOLITES OF VERAPAMIL IN DOG URINE WITH ENANTIOSELECTIVE LIQUID-CHROMATOGRAPHIC TECHNIQUES

The stereochemical composition of verapamil and seven of its basic-ext ractable metabolites, isolated from the urine of dogs administered ora l racemic verapamil, was determined by HPLC, using an Ultron OVM (ovom ucoid) column. One dog was given oral (R)-verapamil alone in order to discriminate the (R)- and (S)-enantiomers of the metabolites. Structur e identification of the isolated verapamil metabolites was accomplishe d using a combination of HPLC-MS and FAB-MS-MS techniques. Six of the urinary verapamil metabolites, including verapamil, were predominantly of the (R)-configuration, whereas one of the metabolites was predomin antly in the (S)-form. The remaining isolated metabolite was comprised of approximately equal amounts of the two forms.