It is unique, Robust, Rapid, Precise, Accurate, Selective and Reproducible RP-HPLC method for simultaneous determination of Chlorpheniramine Maleate, Dextromethorphan Hydrobromide and their related impurities in Cough syrup. This is unique method for determination of impurities in combined dosage form. The separation achieved using phosphate buffer pH 7.20 as mobile phases-A and Mixture of Acetonitrile and methanol as mobile phases on gradient method. The detection wavelength is 225 nm. Flow rate is 0.8mL/minute. Linearity was obtained in the range of LOQ to 150% of limit level concentration, 0.05 μg/mL-0.75 μg/ml for each Dextromethorphan HBr impurity A, B, C and D. The separation achieved on column YMC Triart C18, 250x 4.6 mm, 5μ. The column oven temperature was 40°C and injection volume was 50μL. The Correlation coefficient for all impurities found 1.000. According to ICH guideline Q2(R1) [20], the Method were validated. Using this Chromatographic method, the Impurities determination of both the drug can be achieved easily in single method.