Development of a Stability‐Indicating RP‐HPLC Method for Metformin, Linagliptin, and Dapagliflozin Using Analytical Quality by Design Principles

An AQbD‐driven RP‐HPLC method was developed for the simultaneous estimation of metformin, dapagliflozin, and linagliptin in fixed‐dose pharmaceutical formulations, addressing the analytical challenge posed by their distinct physicochemical profiles. The study introduces novelty by being the first to apply AQbD principles for this three‐drug combination, incorporating risk assessment, systematic optimization, and robust validation in accordance with ICH Q2R2 guidelines. The target was an accurate, precise, and stability‐indicating method suitable for routine quality control. Chromatographic separation was achieved on a C18 column using an acetonitrile‐phosphate buffer mobile phase (pH 6.8, 0.7 mL/min, 30°C, detection at 230 nm). The method displayed excellent linearity ( R 2 > 0.997), with calibration ranges of 20–140 µg/mL for metformin, 0.2–1.4 µg/mL for linagliptin, and 0.6–2.8 µg/mL for dapagliflozin; recovery ranged from 98.9% to 102.3%, and injection repeatability was demonstrated by RSD < 2%. Forced degradation studies confirmed specificity, with clear separation from degradation products and high peak purity indices (> 0.999). Robustness testing using a fractional factorial design showed that the method's performance was unaffected by deliberate parameter changes. In conclusion, the validated AQbD‐based HPLC method is robust, specific, and reliable for the simultaneous quantification and stability assessment of the triple drug formulation and is well‐suited for both regulatory and industrial quality control needs.