The concept of "Quality by Design" (QbD) is getting popularized in pharmaceutical manufacturing industry to understand the product and process to identify the risks involved during manufacturing.  One of the perpetual quality attribute is to have robust analytical method that can provide consistent results though out the life cycle of the product. General considerations during analytical method validation is to perform robustness studies by deliberate changes made in pH of the buffer in mobile phase, change in organic ratio, change in column oven temperature, change in buffer strength and using different column lot numbers etc. However to improve the analytical quality standard, a novel method concept under QbD was introduced which uses single mobile phase for three drug components and estimates using different column chemistries used in pharmaceutical industry viz., C18, C8, phenyl and Cyano column. The validated RP-LC method was successfully applied to the quantitative determination of Chlorpheniramine, Ibuprofen and Pseudoephedrine in tablet dosage form, helping to improve quality control and to assure therapeutic efficacy using all column chemistries.