The main objective of this work was to develop a high performance liquid chromatographic method for the determination of basic compounds present in binary or ternary mixtures in some commercial pharmaceutical products using cation exchange column in place of the conventional reversed phase system and to utilize the experimental design/response surface methodology approach for the development and optimization of these methods. The use of the experimental design methodology enabled developing the methods and finding the optimum separation conditions within short time and with great assurance, thanks to the systematic and sequential nature of the approach as compared with the conventional approach of varying one variable at a time (OVAT) or other non-systematic approaches depending mainly on the knowledge and intuition of the method developer. Since neutral and acidic compounds are either weakly retained or not retained in cation exchange chromatography, this technique renders itself very suitable for the analysis of basic compounds in presence of neutral or acidic compounds without any sample pretreatment.