An efficient HPLC workflow for hydrophilic and lipophilic drug combinations on non-conventional polar stationary phase using bio-solvent

Purpose This study presents a novel testing application for co-elution chromatography of biguanide with two different drug classes, sulfonylurea and sodium-glucose co-transporter 2(SGLT2) inhibitors in tablet dosage form. The focus was to quantitate all three drugs in single run on newer chemistry column, additive free mobile phase, using greener solvent and covering wide concentration range. Method This chromatographic method was established on non-conventional C18- embedded polar shielding(EPS) column, an high-purity silica-based reversed-phase column and a simple mobile phase. This method is environmentally responsible, developed with excellent performance for most metrics of greenness indicated by AGREE score 0.73, BAGI score 80.0, AGREE-Prep score 0.73. MoGAPI score 80 and RAPI score 70.0. It showed sustainability and alignment with most of the principles of green analytical chemistry (GAC). A standardized testing protocol was set for estimating three prominent antidiabetic drugs and to overcome difficulty in estimating low-dose Glimepiride and inconsistent regulatory enforcement. Results The method operated at a column flow rate of 0.8 mL min − 1 with a UV detector at 225 nm. The validated method exhibited excellent linearity within 50–150% of the target concentration with correlation coefficients (r) > 0.99 for all analytes. Accuracy studies showed overall mean recoveries of 99.5% for MTH, 100.1% for GPD and 100.2% for CGF. Conclusion The method is precise, accurate, and environmentally responsible, offering a sustainable analytical approach for simultaneous estimation of three drugs in fixed-dose formulations. It exemplifies the sustainable solvent selection and resource-efficient analytical practices integrated to deliver an accessible greener method.