Mebendazole (Anthelmintic) in combination with Quinfamide (Luminal Amebicide) is extensively used for treatment of Helminthiasis and Amoebiasis.Till present, there is no work found on development of a single combine UPLC method for determination mebendazole and quinfamide with their relative impurities and antioxidants in Fixed dose combination (FDC).The present work describes use of a statistical quality by design approach to develop a robust, stability Indicating, cost-effective and time saving method for simultaneous determination of both APIs with their related impurities and antioxidants by UPLC.Using phase wise screening approach, the final chromatog. conditions employed a Waters Cortecs UPLC C18, 150 mm x 2.1 mm, 1.6μm column with mobile phase consisting of 0.025% Trifluoracetic acid and Acetonitrile/methanol (90:10) in a gradient program.The flow rate and injection volumes were 0.38 mL/min & 2μl, resp., and detection was done at 260 nm.The method was validated according to ICH and ANVISA guidelines.The results evidently reflect that the QbD Approach concept can be effectively applied to develop anal. methods for Fixed dose combinations with fewer trials and error-free experimentation.