A superior method for the estimation of Molnupiravir and its metabolite and degradation product, Beta-D-N4-Hydroxycytidine, in human plasma with dexamethasone

Abstract

Molnupiravir (MOL) is a versatile drug in treating COVID-19. It is activated directly after absorption into D-N4-hydroxycytidine (MET), which resembles the viral substrate cytidine or uridine. Dexamethasone (DEX) is used as an adjuvant medication with MOL to manage symptoms. This work employed microwave irradiation in the hydrolytic degradation of MOL and the synthesis of MET. A white, green, and blue UPLC method was created to estimate the concentrations of MOL, MET, and DEX in human plasma at relevant concentration levels. A BEH® C18 column, a simple mobile phase of acetonitrile and water in a 20:80 ratio, and a flow rate of 0.1 mL/min were employed in the procedure. The antiviral drug favipiravir (FVP) served as the internal standard. The separated drugs were quantified at 230 nm. The validity of the method was justified according to FDA specifications. Performance, greenness, and blueness were compared between the recently created UPLC and the published LC-MS methods. The comparison indicated that our method is greener, bluer, whiter, and more feasible than the published ones. These findings suggest estimating the three medications in human plasma using our proposed method for bioavailability and therapeutic drug monitoring research.