Mathematical spectrophotometric determination of ibuprofen and paracetamol in the presence of 4-aminophenol: AI-assisted comparative assessment

Simple mathematical filtration-based spectrophotometric methods were developed for the selective and accurate simultaneous determination of ibuprofen (IBU), paracetamol (PAR), along with the toxic impurity 4-aminophenol (4-AP) without prior separation. The procedures were implemented using built-in spectrophotometer software through a stepwise approach involving the removal of 4-AP by the ratio subtraction technique, followed by spectral processing of the resolved binary mixture of IBU and PAR. Three spectrophotometric strategies, namely ratio subtraction–constant multiplication (RS-CM), ratio difference (RD), and derivative ratio (DD¹), were established and validated for the quantitative determination of IBU and PAR. The concentration of 4-AP was also quantitatively determined and validated using the concentration-value method (conc. value), with wavelength selection optimized through Artificial Intelligence (AI). The proposed methods exhibited excellent linearity over concentration ranges of 4.0–40.0 µg/mL for IBU, 1.6–16.0 µg/mL for PAR and 1.0–10.0 µg/mL for 4-AP were successfully applied to laboratory prepared mixtures and pharmaceutical formulations. Statistical comparison with reference methods using Student’s t - and F -tests confirmed the accuracy and precision of the proposed procedures. The principal novelty of the study lies in the integrated comparative assessment of the three analytical strategies using the newly introduced Method Performance Score (MPS) and Method Performance Ranking (MPR) systems, which provide quantitative benchmarking of analytical performance. This framework was further complemented by an Environmental, Performance, and Practicality Index (EPPI) and an extended Sustainability of Analytical Methods Index (SAMI) mapped across all 17 United Nations Sustainable Development Goals (SDGs), enabling a multidimensional assessment of analytical performance, practicality, environmental impact, and sustainability. The proposed integrated framework provides a comprehensive basis for selecting an appropriate analytical strategy for routine pharmaceutical quality control.