RP-UPLC method was developed and validated for the determination of chlorpheniramine maleate and dextromethorphan hydrobromide in tablet dosage form. Reverse phase waters acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm) column using isocratic mobile phase of 0.5 mL 0.1% TFA (trifluroacetic acid) in H2O:CH3CN (70:30 %v/v). The flow rate was 0.2 mL/min and 252 nm wavelength use for detection on PDA detector. The retention time of chlorpheniramine maleate was 1.2 min and 2.2 min for dextromethorphan hydrobromide. Chlorpheniramine maleate and dextromethorphan hydrobromide was subjected to stress conditions including acidic, alkaline, oxidation, photolysis and thermal degradation. The method was validated as per ICH guideline with respect to samples to specificity, precision, accuracy, linearity and robustness.