Sustainable and Validated Spectrophotometric Methods for the Analysis of a Ternary Mixture of Cloperastine Fendizoate, Its Degradant, and Methylparaben

Abstract

Methods that include novelty, accuracy, and precision for assessing the manipulation of compounds in a ternary mixture were developed using four spectrophotometric techniques: dual wavelength in ratio spectrum, double divisor-ratio spectra derivative spectrophotometry, derivative ratio zero-crossing, and ratio subtraction. These methods were successfully utilized to quantify a ternary mixture of cloperastine fendizoate (CLOP), its degradation product (Deg), and a hidden preservative, methylparaben (MP), in both their standard forms and pharmaceutical formulation. Each method uniquely measured the analytes, differentiating them by their spectral characteristics. The methods were validated according to the International Council for Harmonization guidelines, demonstrating good linearity. Accuracy was confirmed with mean percentage recoveries ranging from 98.0–102.0%. Experimentally, the absorbance additivity was confirmed to verify the multicomponent analysis by the studied spectrophotometric methods. Statistical comparison between the proposed and reported methods demonstrated no significant difference. To the best of current knowledge, this is the first application of these four spectrophotometric approaches to the simultaneous determination of CLOP, MP, and Deg in Notussil® syrup, and the first direct comparison of their performance under identical conditions. Their advantages over other classical techniques lie in their simplicity, selectivity, efficiency, and low cost. Finally, the environmental sustainability of the proposed methods was evaluated using the analytical eco-scale, green analytical procedure index, and the analytical GREEnness metric tools, and their environmental impact was assessed using the novel white analytical chemistry metric.