A simple, expeditious, and explicit stability-indicating Ultra Performance Liquid Chromatography (UPLC) analytical method was developed and validated for the quantitative analysis of Amitriptyline and Pregabalin in bulk drugs and combined dosage formulations. The method was validated by using Acquity UPLC HSS C18 (100 mm × 1.8 μ) column, the column temperature was maintained at 25°C and the run time 3 min. The mobile phase was a mixture of Mobile Phase: A–Acetonitrile, B–0.1% Ortho Phosphoric acid in water, injection volume of samples was 1 μl and the UV detection λmax at 256 nm. The retention times were discerned as 1.76, 2.11 min and the linearity range was covered from 2.5 μg/ml to 15 μg/ml, 18.75 μg/ml to 112.5 μg/ml of Amitriptyline and Pregabalin respectively. The validation of the method established as per ICH guide lines and the method proved that separation of different degradation products along with the pure drugs were found to be capable of giving swift retention times with fine resolution than that achieved with conventional UPLC. This method exhibited an excellent performance in terms of sensitivity and swift and the results of stress testing was undertaken according to the ICH guidelines reveal that the method is specific and stable and the method has the ability to separate these drugs individually and from their degradation products in solid dosage forms and hence this method can be used for routine analysis in quality control.