Development of an environmentally friendly RP-HPLC method for the concurrent determination of sitagliptin and metformin in bulk and tablets dosage forms using an analytical Quality by Design approach: sustainability and greenness rules for appraisal

For highly specific quantitation in pharmaceutical combinations, high-performance liquid chromatography (HPLC) is the recommended technique. Using the Quality by Design approach (QbD) approach, this study created and verified an eco-friendly reversed-phase HPLC technique for the simultaneous separation and measurement of sitagliptin (STG) and metformin (MTF) in tablets. The technique used an Inertsil USP L10 (250 × 4.6 mm, 5 µm) Cyano Column as the packing material, a gradient mode (51:49) eluent consisting of ethanol and 30 mM monobasic monopotassium phosphate buffer (pH 4.5), an injection volume of 20.0 µL, a flow rate of 1.0 mL/min, and UV-detection at 265 nm and 233 nm for STG and MTF, respectively, at 25°C. According to ICH Q2(R1) standards, validation was carried out. For STG, the linearity ranges were 50–150 µg/mL, while for MTF, they were 5–15 µg/mL (R2 ≥ 0.9998). AGREE—Analytical GREEnness Metric Approach (0.78), AES—Analytical Eco-scale (92), RGB12 (Red-Green-Blue 12) (80.5%), BAGI—Blue applicability grade index (82.5), Environmentally Sustainable Analytical Workflow Index GAPI—Green Analytical Procedure Index, and the carbon footprint (0.000968) were among the indicators used to numerically evaluate the method's eco-sustainability. This approach was shown to be appropriate for the simultaneous measurement of MTF and STG in commercial tablets and was time-efficient, cost-effective, quick, durable, rugged, precise, and accurate.