Balancing performance and sustainability: a white differential pulse voltammetry method for metformin and empagliflozin in plasma

Background Simultaneous therapeutic drug monitoring of metformin (MEF) and empagliflozin (EMP) in plasma requires sustainable, white analytical chemistry (WAC) methods. Existing techniques suffer from poor greenness, electrode modification complexity, and limited plasma applicability.Research design and methods White/green differential pulse voltammetry (DPV) method developed using unmodified glassy carbon electrode (GCE). Protein precipitation (acetonitrile) from ethically sourced blank human plasma (BUC-IACUCPHA183A/2025). Optimized: phosphate buffer pH 7, 75 mV/s scan rate. Validated per ICH Q2(R1) across linearity, LOD/LOQ, accuracy, precision, specificity (n = 9).Results Linearity: MEF 20–60 μM (r = 0.997), EMP 10–70 μM (r = 0.997). LODs: 4.38 μM (MEF), 4.15 μM (EMP). Plasma recoveries: 99.4 ± 1.5% (MEF), 100.4 ± 1.4% (EMP), n = 5. Whiteness: 97/100 (RGB-12); greenness: 83/100 (MOGABI) – superior to reported methods.Conclusions Validated DPV-GCE enables rapid, sustainable MEF/EMP quantification in plasma without modification/chromatography. Proof-of-concept for routine therapeutic monitoring; clinical translation limited by spiked (not patient) samples