Bridging MOE with eco-friendly chromatographic analyses of metformin and ursodeoxycholic acid with their official impurities: Multi-metric sustainability assessment

In response to the increasing demand for sustainable and reliable analytical approaches, this study presents the development of two environmentally friendly, selective, and robust chromatographic methods for the concurrent determination of metformin and ursodeoxycholic acid in the presence of their pharmacopeial impurities. HPLC-DAD method (Method I) employed C8 column using a gradient elution of phosphate buffer (pH 2.5), methanol, and acetonitrile, achieving baseline separation of seven analytes within 15 min at a detection wavelength of 210 nm. HPTLC method (Method II) utilized silica gel plates with a benign biobased mobile phase (ethyl acetate, ethanol, water, and acetic acid). It quantified Melamine and cyanoguanidine at 211 nm, metformin at 236 nm, and following derivatization with p-anisaldehyde, ursodeoxycholic acid and cholic acid at 533 nm. The proposed HPTLC method failed in complete separation of chenodeoxycholic acid and deoxycholic acid from ursodeoxycholic acid, whereas the HPLC-DAD method provided full resolution of all analytes. To rationalize the observed separation patterns, molecular docking simulations were performed using MOE software. Both methods were validated according to the guidelines of the International Council for Harmonization (ICH). They were successfully applied to laboratory made and spiked dosage forms without interference from excipients. Additionally, they were thoroughly assessed using multiple modern frameworks (tetra-color assessment), which collectively considered analytical performance, economic practicality, and eco-friendliness. The study also evaluated the alignment with the United States Sustainable Development Goals, confirming their status as sustainable, practical, cost-effective, and robust tools for routine quality control of the two drugs and their official impurities.