The analysis of weakly basic drugs such as verapamil by reverse-phase liquid chromatography remains a problem, particularly when present in combination with other drugs such as amphoteric compounds like trandolapril. In this study, the simple, accurate, precise and fully validated RP-LC method for the simultaneous determination of verapamil and trandolapril in combined dosage forms has been developed. The LC method allowed quantitation over the ranges of 0.50-18.00 μg/mL and 0.05-1.00μg/mL for verapamil and trandolapril, respectively. The detection limits were found to be 0.008μg/mL and 0.018μg/mL for verapamil and trandolapril, respectively. Moreover, pKa values of verapamil and trandolapril were determined via the dependence of the retention factor on the pH of the mobile phase for ionizable substances. The effect of the mobile phase composition on the ionization constant was studied by measuring the pKa at different methanol-water mixtures, ranging 50-65% (v/v). It was shown that RP-HPLC was sllitab1e for the high throughput analysis of the combination of verapamil and trandolapril. The method also allows a number of cost and time saving benefits and can be readily employed for the analysis of pharmaceutical formulations. The method has been verified, without any interference from excipients, for the concurrent analysis of these compounds in tablets.