Innovative UPLC technique for concurrent quantification of etofenamate and benzyl nicotinate in the presence of methylparaben and benzyl alcohol in their topical cream: Greens, white, and Six Sigma methodologies

The efficacious treatment of muscle and joint pain relies heavily on etofenamate (ETO) and benzyl nicotinate (BN), which possess robust anti-inflammatory and pain-relieving properties when paired with methylparaben (MP) or benzyl alcohol (BA). In this study, we have established and validated innovative RP-UPLC methods for assessing ETO and BN in the presence of MP or BA in their dosage forms, employing eight green tools to evaluate their eco-friendliness and effectiveness. Reversed phase-ultra-performance liquid chromatography (RP-UPLC) technique employs a flow rate of 0.3 mL/min on Waters Acquity UPLC BEH Column (C18, 1.7 μm, 100 mm × 2.1 mm), detection at 254 nm using a photo diode array (PDA) detector and mobile phase of 0.05 M KH₂PO₄ buffer, acetonitrile, and methanol (50:15:35, v/v/v) adjusted pH 6.0 with 0.2% triethylamine. For ETO, BN, MP, and BA, the calibration curves were linear and ranged from 0.005 to 1.0, from 0.001 to 0.2, from 0.002 to 0.08, and from 0.0001 to 0.1 mg/mL, respectively. The correlation value was 0.9999, and the accuracy findings ranged from 98.81% to 100.56%. Consequently, the methodology has been successfully implemented in assay testing for the pharmaceuticals in the presence of the MP or BA, demonstrating the high selectivity of these approaches. The present study presents the Blue Applicability Grade Index (BAGI), an innovative approach that complements green metrics in practical white analytical chemistry. According to the International Council for Harmonisation (ICH) criteria, the procedures were effectively validated.