Eco-sustainable organic solvent-free spectrophotometric method for the concurrent determination of a ternary pharmaceutical mixture

In recent years, green analytical chemistry has become essential in pharmaceutical research, aiming to mitigate environmental hazards associated with conventional analytical practices. The current focus lies in optimizing analytical methods to achieve both environmental and economic sustainability. In this framework, three environmentally sustainable spectrophotometric methods were developed for simultaneous analysis of three co-formulated drugs: acetaminophen, dextromethorphan hydrobromide, and pseudoephedrine hydrochloride, which are often used to alleviate symptoms associated with COVID-19. The employed spectrophotometric methodologies include the double divisor-ratio spectra derivative method, the mean centering of double divisor ratio spectra method, and the dual wavelength in ratio spectrum method. The innovative techniques displayed good linearity within 25–350 µg/mL for dextromethorphan hydrobromide, 2–24 µg/mL for acetaminophen, and 100–1400 µg/mL for pseudoephedrine hydrochloride. The environmental sustainability of the proposed methods was evaluated using the Analytical Eco-Scale, analytical greenness metric, and the Green Analytical Procedure Index. Furthermore, complementary evaluations of blueness and whiteness were conducted through the Blue Applicability Grade Index and the Red Green Blue 12 metric, respectively. The collective outcomes of all evaluation metrics clearly demonstrated that the proposed methods possess enhanced environmental compatibility and sustainability relative to the existing techniques. The proposed methods were fully validated according to the International Conference on Harmonization recommendations. The developed methods offered a cost-effective and eco-friendly approach for concurrent determination of acetaminophen, dextromethorphan hydrobromide, and pseudoephedrine hydrochloride in their bulk substances, and pharmaceutical formulations.