An RP-HPLC method for the simultaneous determination of Pseudoephedrine, Guaiphenesin, Ambroxol and Chlorpheniramine Maleate in syrup was developed and validated as per ICH & FDA guidelines. The separation was achieved with a Hypersil BDS C18, 5μm, 100 mm x 4.6 mm, by using a isocratic system at 215 nm. The mobile phase was prepared with Buffer (0.007 mM/L of KH2PO4 adjusted pH 3.0 with Orthophosphoric acid) and Acetonitrile in ratio (78:22) v/v. The flow rate was 0.8 mL/min and column temperature was maintained at 300C. The separation was achieved within 12 minutes. The linearity of the proposed method was investigated in the range 0.02404-0.03606 mg/mL (r= 0.999) for Pseudoephedrine, 0.04002-0.06002mg/mL (r= 1.000) for Guaiphenesin, 0.01202-0.01804mg/mL (r= 1.000) for Ambroxol, and 0.00162-0.00242 mg/mL (r= 0.998) for Chlorpheniramine. Blank and placebo did not disturb the detection of Pseudoephedrine, Guaiphenesin, Ambroxol, and Chlorpheniramine. The developed method has an advantage that all the drugs can be quantified alone or in combination using a single mobile phase.