High-performance liquid chromatography (HPLC) method was developed and optimized to separate metformin hydrochloride, sitagliptin phosphate monohydrate, linagliptin, empagliflozin, and vonoprazan fumarate in bulk and pharmaceutical formulations. A Hypersil BDS C8 column (150 × 4.6 mm, 4.5 µm) served as the stationary phase for chromatographic separation. The mobile phase contained 0.03 M phosphate buffer, heptane sulfonate, and methanol (55:45, v/v) at pH 7, with a flow rate of 1 mL/min. Detection was carried out at 210 nm, ensuring maximum sensitivity and selectivity. The chromatographic settings were optimized to provide effective sepa￾ration and good analyte resolution. Method validation by International Council for Harmonization (ICH) re￾quirements, yielded good correlation coefficients, accuracy, and precision, verifying the suggested method’s dependability and robustness. Furthermore, an evaluation of the method’s environmental impact using the Analytical eco-scale, Green Analytical Procedure Index (GAPI), and Analytical GREEnness Calculator (AGREE) demonstrated its viability as an environmentally benign methodology. Blue Applicability Grade Index (BAGI), and whiteness assessments verified the method’s applicability, highlighting its potential for regular pharma￾ceutical analysis