Quantification of paracetamol and flupirtine maleate in tablet formulation by application of spectral modification and principle component regression techniques using R programming

Abstract

The present study describes the development of four complementary UV spectrophotometric approaches for the simultaneous quantification of paracetamol (PM) and flupirtine maleate (FU) in combined tablet dosage forms exhibiting extensive spectral overlap. Three ratio spectrum-based methods, namely ratio difference (RD), mean centering (MC), and ratio derivative spectroscopy (RDS), together with a chemometric principal component regression (PCR) model developed using R programming, were investigated to provide simple, rapid, and economical alternatives to chromatographic methods. The developed methods effectively resolved the overlapping spectra of PM and FU without prior separation and were successfully applied to the analysis of laboratory-prepared mixtures and commercial tablet formulations. The resolving capability of the MC and RDS methods was further verified through spectral purity assessment using the spectral contrast angle (cos θ) and spectral ratio factor (SRF). The proposed methods were validated in accordance with ICH Q2(R2) guidelines and demonstrated satisfactory specificity, linearity, accuracy, precision, robustness, and assay performance over the investigated concentration ranges. Statistical comparison with a validated HPLC reference method using Student’s t -test and F -test confirmed that no statistically significant differences existed between the proposed methods and the reference method at the 95% confidence level. Furthermore, greenness assessment using AGREE and Complex GAPI indicated that the proposed methods offer superior environmental performance compared with reported chromatographic procedures. The combination of ratio spectrum manipulation techniques and chemometric modelling provides reliable, cost-effective, and environmentally friendly analytical alternatives for the routine quality control of PM and FU in pharmaceutical dosage forms.