QBD-Based Analytical Method Development and Validation for the Simultaneous Estimation of Voglibose and Metformin Using RP-HPLC

Abstract

A scientifically rigorous and precise reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed using a Quality by Design (QbD) approach for the simultaneous estimation of Voglibose and Metformin in fixed-dose combination formulations. The method was systematically optimized through Design of Experiments (DoE), evaluating critical parameters such as flow rate, buffer pH, and organic solvent ratio for their impact on chromatographic responses like resolution and tailing factor. Statistical analysis via ANOVA confirmed the significance of the quadratic model in achieving optimal separation. The final method employed a Zorbax C18 column with phosphate buffer (pH 4.5) and acetonitrile (45:55 v/v) as the mobile phase, operating at a flow rate of 1.2 mL/min and detection at 225 nm. This setup yielded excellent peak separation with a resolution of 10.10 between the analytes. Validation was conducted in accordance with ICH Q2(R1) guidelines, demonstrating outstanding linearity for Metformin (25–125 µg/mL) and Voglibose (0.1–0.5µg/mL), with correlation coefficients of 0.9998 and 0.9994, respectively. Precision studies confirmed repeatability and intermediate precision (%RSD < 2%), while accuracy was validated through high recovery rates (99.4% for Voglibose and 99.6% for Metformin). Sensitivity was affirmed with acceptable LOD and LOQ values. This QbD-driven RP-HPLC method provides a robust, validated, and regulatory-compliant solution for simultaneous estimation of Voglibose and Metformin in pharmaceutical applications