Design‐of‐Experiments Optimized Micellar Electrokinetic Chromatography Method for the Simultaneous Determination of Dapagliflozin and Metformin in Pharmaceutical Formulations

ABSTRACT

A micellar electrokinetic chromatography (MEKC) method was developed and validated for the simultaneous determination of dapagliflozin (DAPA) and metformin (MET) in pharmaceutical formulations. Due to the markedly different physicochemical properties of the two antidiabetic drugs, conventional capillary zone electrophoresis failed to provide adequate selectivity. This limitation was overcome by introducing MEKC, enabling the selective separation of a neutral and a highly polar cationic analyte. Following an initial one‐factor‐at‐a‐time screening, critical experimental parameters were systematically optimized using a Box–Behnken design, evaluating the influence of sodium dodecyl sulfate (SDS) concentration, separation voltage, and capillary temperature on DAPA migration time, MET peak symmetry, and generated current. Optimized separation was achieved using a 25 mM borax buffer (pH 9.3) containing 38 mM SDS, a separation voltage of 28 kV, and a capillary temperature of 25°C, with ultraviolet detection at 210 nm. Under these conditions, complete separation was obtained within 7 min. The method exhibited good linearity over concentration ranges of 0.02–0.20 mg mL ^{− 1} for DAPA and 0.1–1.00 mg mL ^{− 1} for MET, with satisfactory precision, accuracy, and sensitivity. Robustness evaluation using a Plackett–Burman design confirmed the stability of the method. The method was successfully applied to the analysis of commercial fixed‐dose combination tablets, yielding assay results consistent with labeled claims. The developed method represents a rapid, reliable, and environmentally favorable alternative to conventional chromatographic approaches for the routine quality control of fixed‐dose antidiabetic formulations.