QBD driven analytical method development and validation of metformin and dapagliflozin by using reverse phase-high performance liquid chromatography

Abstract

A simple, sensitive, precise, accurate, and robust, high-performance liquid chromatographic method has been developed to simultaneously estimate Metformin (MET) and Dapagliflozin (DAPA) in pharmaceutical formulation. Design of experiments (DoE) was applied for multivariate optimization of the experimental conditions of the RP-HPLC method. A risk assessment was performed to identify the critical method parameters. The mobile phase composition, flow rate, and column temperature were used to design mathematical models. Box Behnken design (BBD) was used to study the response surface methodology and the effects of these independent factors. The desirability function was used to simultaneously optimize the retention time and resolution of MET and DAPA. The optimized and predicted data from the contour diagram consisted of acetonitrile and ortho phosphoric acid (0.1%) in the ratio of 50:50, respectively, at a flow rate of 1.0 ml/min and column temperature 29°C. Using these optimum conditions, baseline separation of both drugs with good resolution and run time of less than 5 min were achieved. The optimized assay conditions were validated according to ICH guidelines. Hence, the results clearly showed that the Quality by design approach could be successfully applied to optimize the RP-HPLC method for simultaneous estimation of MET and DAPA.