Comparative study of Normal-phase versus reversed-phase HPTLC methods for the concurrent quantification of three antiviral agents against COVID19: Remdesivir, favipiravir and Molnupiravir: trichromatic sustainability assessment.

The pursuit of sustainability in analytical chemistry is a multifaceted, challenging and complex endeavor. This requires continuous and competitive attempts to achieve the sustainable development goals at every step of the analytical methodology by adhering to the principles of green, blue and white analytical chemistry. This also involves assessment of the degree of sustainability using the latest evaluation metrics until finally reaching the design of a trichromatic procedure. The herein illustrated work represents a comparative study between two newly developed normal-phase and reverse-phase HPTLC methods for the simultaneous quantitative determination of Remdesivir (RMD), Favipiravir (FAV) and Molnupiravir (MOL). For normal-phase HPTLC method, the employed mobile phase consisted of ethyl acetate: ethanol: water (9.4:0.4:0.25, v/v), while, for reverse-phase HPTLC procedure, a greener mobile phase was employed consisting of ethanol: water (6:4, v/v). For both methods, detection wavelength of RMD and MOL was 244 nm while FAV was detected at 325 nm. Both methods were validated following the International Council for Harmonisation (ICH) guidelines with respect to linearity, range, accuracy, precision and robustness. The two established methods were proved to be linear over the range of 50-2000 ng/band for FAV and MOL and over the range of 30-800 ng/band for RMD. The excellent linearities were proved by the high values of correlation coefficients not less than 0.99988. The developed methods were successfully applied for the determination of the three drugs in their bulk form and in their pharmaceutical formulations. Furthermore, a thorough comparative and integrative trichromatic evaluation of sustainability of the designed methods was performed. The Analytical Eco-Scale, the novel Modified Green Analytical Procedure Index (MoGAPI) (2024) and the Analytical GREEnness (AGREE) metrics were applied for greenness assessment and the recent Blue Applicability Grade Index (BAGI) (2023) tool was employed for blueness evaluation. Finally, the RGB12 model was implemented for appraisal of whiteness of the developed methods.