Fedorov algorithm–optimized chemometric spectrophotometry for cefepime–tazobactam microanalysis in plasma and pharmaceuticals with integrated MA and NQS sustainability assessment

Abstract

Abstract A green, sustainability-oriented chemometric-assisted UV spectrophotometric platform was developed for the simultaneous determination of Cefepime (CFPM) and Tazobactam (TAZO) in pharmaceutical formulations and human plasma. Water served as the sole diluent, eliminating hazardous organic solvents and substantially reducing the environmental impact of the analytical procedure. Calibration and validation sets were efficiently constructed using the Fedorov exchange algorithm within Brereton’s multilevel design framework, yielding 25 calibration and 13 validation mixtures and reducing experimental workload by approximately 70% compared with conventional designs. Three complementary chemometric models were evaluated: Principal Component Regression (PCR), Firefly Algorithm–assisted Partial Least Squares (FA-PLS), and Multivariate Curve Resolution–Alternating Least Squares (MCR-ALS). Among them, MCR-ALS demonstrated superior predictive performance, with correlation coefficients exceeding 0.9998 for both analytes, minimal systematic bias confirmed by Elliptical Joint Confidence Region analysis, and high robustness across pharmaceutical and plasma matrices. Limits of detection were 0.0487 and 0.0396 µg mL –1 , while limits of quantification were 0.1476 and 0.1200 µg mL –1 for CFPM and TAZO, respectively. The method was validated in accordance with ICH guidelines and successfully applied to CEFE-MAX™ powder for injection and fortified human plasma. Matrix effect evaluation showed negligible signal suppression (− 2.35% to − 1.27%), indicating strong matrix tolerance and calibration transferability. Comparative benchmarking against reported HPLC–UV, LC–MS/MS, capillary zone electrophoresis, and UV spectrophotometric methods demonstrated that the proposed approach achieves an optimal balance of sensitivity, simplicity, and environmental sustainability. Sustainability assessment using the Multi-Color Assessment (MA), carbon footprint analysis, and the Need–Quality–Sustainability (NQS) index yielded a Whiteness Score of 83.6%, an NQS score of 90, and a low carbon footprint of 0.032 kg CO₂-eq per analysis. Overall, the developed platform provides a rapid, cost-effective, and environmentally responsible alternative for routine quality control and preliminary therapeutic monitoring of the CFPM–TAZO combination.