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

Abstract

Background Common cold and cough preparations represent a huge segment of global pharmaceutical market. Recently, cold/cough formulations containing Paracetamol (PAR) have attracted a significant attention due to PAR has been implemented into the supportive treatment of COVID-19 mild cases as the first line antipyretic. According to the literature review, no method has been reported yet for simultaneous estimation of PAR, Pseudoephedrine hydrochloride (PSE) and Carbinoxamine maleate (CRX) in any matrices. Thus, there is an urgent need for smart, and green methods that would enable quantification of the cited components in their desperate 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 constant multiplication method paired with spectrum subtraction. Results These methods were linear over the concentration range of 2.5–35 μg/mL, 1.5–20 μg/mL and 4.5–35 μg/mL for PAR, PSE and CRX, respectively. These methods fulfill the validity parameters according to ICH guidelines. The obtained results were statistically benchmarked to the official ones where no significant difference was noticed. Conclusion The developed methods are successfully applied for concurrent quantification of 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 AGREE algorithm based on the green analytical chemistry framework, GAPI, Eco-Scale, AGP, and NEMI. Highlights Green spectrophotometric methods on simultaneous quantification of PAR, PSE and CRX for the first time. These approaches incorporate simple enrichment-aided technique to augment their spectrophotometric signals facilitating the accurate quantitation of the minor component in the cited mixture.