Analytical Quality‐by‐Design‐Oriented High‐Performance Liquid Chromatographic Method for Quantification of Metformin Hydrochloride, Teneligliptin Hydrobromide Hydrate and Dapagliflozin in Tablet Dosage Form

ABSTRACT High‐performance liquid chromatography method was optimized using the analytical quality‐by‐design strategy to provide robust, efficient, and reproducible analysis. This study aimed to define an analytical target profile with the identification of critical quality attributes by risk priority number. Further, a Box–Behnken design was used for optimization of critical method variables: volume of buffer, flow rate, and temperature. Separation was achieved using Inertsil ODS 3 V (250 mm × 4.6 mm i.d., 5 µm), using a mobile phase ratio of dipotassium hydrogen phosphate buffer (pH 6):methanol:acetonitrile (38:52:10 % v/v/v) at 0.9 mL/min, and detection was carried out at 233 nm. Retention times for metformin hydrochloride, teneligliptin hydrobromide hydrate, and dapagliflozin were 2.78, 8.22, and 11.60 min, respectively. The concentration ranges for metformin hydrochloride, teneligliptin hydrobromide hydrate, and dapagliflozin were 150–450, 6–18, and 3–9 µg/mL, respectively. For metformin hydrochloride, teneligliptin hydrobromide hydrate, and dapagliflozin, the lower detection limits were 11.08, 0.70, and 0.35, and the lower quantification limits were 33.58, 2.12, and 1.08 µg/mL, respectively, showing the sensitivity of the method. For accuracy determination, the percentage recoveries for metformin hydrochloride, teneligliptin hydrobromide hydrate, and dapagliflozin were determined to be in the ranges of 98.64%–101.28%, 98.61%–101.8%, and 100.44%–101.4%, respectively. Based on the design results and statistical analysis, suitable operating parameters for each critical method parameter, including flow rate (0.85–0.95 mL/min), buffer volume (37–39 mL), and column temperature (45°C–49°C), were established to consistently produce acceptable outcomes. The suggested approach was evaluated with green evaluation tools such as AGREEprep, MoGAPI, BAGI, and analytical Eco‐scale. Thus, this proposed method provides regular analysis of metformin hydrochloride, teneligliptin hydrobromide hydrate, and dapagliflozin in pharmaceutical formulations and bulk drugs without any environmental impact.