Optimization and validation of UPLC method for dapagliflozin and candesartan cilexetil in an on-demand formulation: Analytical quality by design approach

Abstract The coincidence of hypertension and diabetes mellitus represents a significant medical challenge in clinical settings. This relates to high risks of target organ damage and increased cardiovascular morbidity and mortality. Therefore, there is an urgent demand for developing pharmaceutical formulations containing drug combinations with potential synergistic effects. A combination of dapagliflozin (DPA) and candesartan cilexetil (CND) was proposed due to their complementary mechanisms in managing both conditions. To ensure quality control of this combination, a novel ultra performance liquid chromatography method was developed and validated for simultaneous quantification of both drugs using Quality by Design approach. The impact of flow rate (0.2–0.4 mL/min) and aqueous phase ratio (55–65%) on chromatographic parameters was evaluated using Design of Experiment Central Composite Design. The optimized conditions with 0.2 mL/min flow rate and 55% aqueous phase ratio achieved effective separation with retention times of 1.46 and 4.30 min for DPA and CND, respectively, using C18 Acquity BEH column (2.1 mm × 50 mm, 1.8 µm). The method demonstrated linearity over 0.3–50.0 μg/mL for DPA ( R 2 = 0.9999) and 0.1–50.0 μg/mL for CND ( R 2 = 0.9999). Lower limits of quantification were 0.9 and 0.5 μg/mL for DPA and CND, respectively. Intra-day and inter-day precision values were below 8% relative standard deviation, with accuracy ranging from 94.2–104.4%. The validated method was successfully applied to quantify both drugs in marketed tablet formulations, demonstrating its practical utility for pharmaceutical quality control.