Chemometric-Assisted spectrophotometric method for the simultaneous determination of metformin, gliclazide and glibenclamide in bulk and pharmaceutical formulations

Background: Multivariate chemometric calibration methods are useful for simultaneous determination of drugs with overlapping spectra. Metformin (MET), gliclazide (GLZ), and glibenclamide (GLN) are commonly used antidiabetic drugs that require accurate and sensitive quantification. Objective: To develop and validate rapid, precise, and sensitive PCR and PLS models for the simultaneous determination of MET, GLZ, and GLN in synthetic mixtures. Method: PCR and PLS models were developed using a calibration set and evaluated by cross-validation and an external validation set. Absorption spectra were recorded from 200–400 nm, covering MET, GLZ, and GLN concentration ranges of 0.8–2 µg/mL, 1–8 µg/mL, and 1–6 µg/mL, respectively. The models were validated according to ICH guidelines. Results: The PCR and PLS models showed excellent performance, with RMSEP values of 0.047–0.048 for MET, 0.0216–0.093 for GLZ, and 0.0319–0.051 for GLN. Correlation coefficients ranged from 0.9996–0.9998, accuracy was 98.6–100.4%, and RSD < 2%. LOD and LOQ were 0.032–0.087 µg/mL and 0.091–0.139 µg/mL, respectively. The methods were successfully applied to synthetic mixtures of commercial dosage forms.LOD: 0.0321–0.087 µg/mL, LOQ: 0.0907–0.1387 µg/mL. Conclusions: PCR and PLS models are rapid, accurate, precise, and sensitive methods for simultaneous quantification of MET, GLZ, and GLN, suitable for routine quality control in pharmaceutical analysis.