Determination of verapamil and norverapamil in human biological material. Investigation of plasma concentrations after oral administration of two different verapamil formulations.

A method for the simultaneous determination of the cardiovascular agent verapamil and its major metabolite norverapamil in human plasma is described. Analysis is performed after alkaline extraction with n-heptane by subsequent ion-paired high performance liquid chromatographic (HPLC) separation, and direct fluorimetric measurement of both compounds (lambda maxex. = 278 nm, lambda maxem. = 320 nm). The sensitivity of the procedure (detection limit less than 1 ng/ml) is suitable for pharmacokinetic studies after therapeutic doses. The applicability of the method was tested by performing a clinical study. Plasma concentrations of two verapamil formulations for oral administration were examined. The active metabolite norverapamil was included in the investigation.