A new simple, rapid, and sensitive liquid chromatographic method has been developed and validated for the simultaneous determination of caffeine, paracetamol, pseudoephedrine, aspirin, dextromethorphan, and chlorpheniramine in pharmaceutical tablet formulations and was performed on conventional C 18 and monolithic silica C 18 columns. Chromatographic separation was achieved by using a mixture of methanol and a buffer containing 10mM NaH 2PO 4, 3mM heptane sulfonic acid sodium salt, 0.1% triethylamine, pH 2.5 (adjusted with hydrochloric acid) in a ratio 50:50v/v, 40:60v/v for conventional C 18 and monolithic silica C 18 columns, respectively. Quantitation was achieved with UV detection at 214nm, based on peak area. The proposed method could be used in the presence of salicylic acid as impurity or decomposition product in dosage forms containing aspirin. The proposed method was validated and successfully applied for the analysis of pharmaceutical formulations and laboratory-prepared mixtures containing these multicomponent combinations.