RP-HPLC-PDA method has been developed and validated for quantitative determination of ROSUVASTATIN and AMLODIPINE from tablet formulations. All the parameters for the two titled drugs met the criteria of ICH guidelines for method validation. As the mobile phase is MS compatible then method can be used to determine analytes individually or in combination in biological fluids to study the pharmacokinetics and used for LC-MS system. The method is very simple, rapid and economic in nature as all peaks are well separated, which makes it especially suitable for routine quality control analysis work. Symmetrical peaks were obtained through experimental trials. Two columns were used for performance investigations, including Kromasil C18 (5 micron 4.6 × 250mm) and Qualisil C8 (5 micron 4.6 × 250mm), the first column was the most suitable one since it produced symmetrical peaks with high resolution. The UV detector response of ROSUVASTATIN and AMLODIPINE was studied and the best wavelength was found to be 251 nm showing highest sensitivity. Several modifications in the mobile phase composition were made in order to study the possibilities of changing the selectivity of the chromatographic system. These modifications included the change of the type and ratio of the organic modifier, pH, flow rate, temperature and stability of ROSUVASTATIN and AMLODIPINE were also studied in methanol and mobile phase.