This study Includes innovation and validation of RP-HPLC method for determination of the drugs Chlorpheniramine maleate(Chlor) , Phenylphrine HCl(Phen), Glyceryl guaiacolate(Gly), and the additives Methyl paraben)M.H.B),Propyl paraben(P.H.B) and Yellow dye no.6 by using of L11 column(25cm×4.6mm,5µm) and mobile phase content of Methanol : water 60:40(v/v) containing 300mg Sodium dihydrogen phosphate , 9 ml Solution of Triethylamine hydrochloride, 300mg Sodium lauryl sulfate, and pH 3.5 the detection was at 269 nm. The method successfully applied to determination of all drugs in pure and in pharmaceutical forms. Rec% was between 95.2677-104.0223, RSD% was between 0.00004-0.0140, LOD was between 0.0001-0.0015µg/ml and LOQ was between 0.0003-0.0045 µg/ml. [ABSTRACT FROM AUTHOR]