Eco-friendly stability-indicating HPTLC micro-determination of the first FDA approved SARS-CoV-2 antiviral prodrug Remdesivir: Study of degradation kinetics and structural elucidation of the degradants using HPTLC-MS

Abstract

The worldwide spread coronavirus (covid-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents a global health crisis. The world was forced to face a great challenge to control and overcome this health disaster through various containment measures including efficient vaccination side by side with effective medication. Remdesivir (RMD) is the first FDA approved antiviral agent for treatment of covid-19 pandemic and hence regarded as the first-in-class medication of this highly contagious respiratory disease. The current study represents the first stability indicating HPTLC method for the estimation of RMD in bulk form and pharmaceutical formulation. The method employed TLC silica gel aluminum plates 60 F254 as stationary phase and green mobile phase composed of ethyl acetate and ethanol (96: 4, v/v) with densitometric detection at 245 nm. Comprehensive validation of the adopted method was accomplished according to the ICH guidelines regarding linearity, ranges, detection and quantification limits, precision, accuracy and robustness. The developed method offered a neat separation of the drug in presence of pharmaceutical excipients as well as in presence of acidic, alkaline, neutral hydrolytic, oxidative and photolytic degradants. Additionally, structural elucidation of alkaline and hydrolytic oxidation degradation products was carried out using HPTLC-MS. Furthermore, for the first time the acidic and alkaline degradation kinetics of RMD were studied and its degradation rate constants and half-lives were calculated. Moreover, greenness appraisal of the developed method as well as comparison with previously published stability indicating HPLC methods were performed using analytical Eco-scale, GAPI and AGREE metrics.