Objectives: As per requisition of current regulatory requirements, simple, rapid and sensitive method by 33 factorial QbD approach was established and validated for Levosulpiride and Ilaprazole by RP-HPLC. Method: A simple RP-HPLC  method  has  been  developed  and  validated  with different  parameters  such  as  linearity,  precision,  repeatability, LOD, LOQ,  accuracy  as  per ICH guidelines (Q2R1). Statistical data analysis was done for data obtained from different aliquots Runs on Agilent Tech. Gradient System with Auto injector, UV (DAD) & Gradient Detector. Results: Equipped with Reverse Phase (Agilent) C18 column (4.6mm x 250mm; 5µm), a 20µl injection loop and UV730D Absorbance detector at 219 nm wave length and running chemstation 10.1 software and drugs along with degradants were separated via Methanol: (0.1% OPA) Water (45:55) of pH 3.2 as mobile phase setting flow rate 0.6 ml/min at ambient temperature, retention time at 4.257 min and 5.547 min. with good peak shape (Theoretical plates of 6972 of Levosulpiride and 3521 of Ilaprazole). The LOD and LOQ of Levosulpiride were found to be 1.8208μg/ml and 5.5176μg/ml. The LOD and LOQ of Ilaprazole were found to be 0.3676μg/ml and 1.1139 μg/ml analytical method that concluded.