Novel Spectrophotometric Approaches for the Simultaneous Quantification of Ternary Common Cold Mixture Containing Paracetamol with a Challenging Formulation Ratio: Greenness Profile Evaluation

Background Common cold and cough preparations represent a huge segment of the global pharmaceutical market. Recently, cold/cough formulations containing paracetamol (PAR) have attracted significant attention as PAR has been implemented into the supportive treatment of mild cases of COVID-19 as the first-line antipyretic. From a literature review, no method has been reported yet for simultaneous estimation of PAR, pseudoephedrine hydrochloride (PSE) and carbinoxamine maleate (CRX) in any matrix. Thus, there is an urgent need for smart and green methods that would enable quantification of the cited components in their challenging ratio. Objectives The aim of this work is to develop and validate the first UV spectrophotometric methods for simultaneous determination of the selected drugs taking into consideration the list of challenges including the highly overlapping features and spectral interferences in the cited mixture. Methods Namely, the proposed methods are: direct spectrophotometry, dual wavelength, first derivative, derivative ratio, ratio difference, constant center coupled with spectrum subtraction, and the constant multiplication method paired with spectrum subtraction. Results These methods were linear over the concentration range of 2.5-35 mu g/mL, 1.5-20 mu g/mL, and 4.5-35 mu g/mL for PAR, PSE and CRX, respectively. These methods fulfill the validity parameters according to International Conference on Harmonization (ICH) guidelines. The results obtained were statistically benchmarked to the official ones where no significant difference was noticed. Conclusion The developed methods are successfully applied for concurrent quantification of the studied components in the marketed dosage form without interference from matrix excipients. The impact on the environment was assessed by five green metrics, namely a recent Analytical greenness (AGREE) metric algorithm based on the green analytical chemistry framework, Green Analytical Procedure Index (GAPI), Eco-Scale, Assessment of Green Profile (AGP), and National Environmental Methods Index (NEMI).

Automated summary

This study developed and validated the first UV spectrophotometric methods for simultaneous determination of selected drugs, addressing the challenges of overlapping features and spectral interferences. These methods were successfully applied to quantify the studied components in marketed dosage forms, demonstrating their effectiveness in concurrent quantification.