Determination and structural characterization of ravidasvir metabolites by liquid chromatography coupled to triple quadrupole linear ion trap mass spectrometry: Application to pharmacokinetics and phase I metabolism in rats.

Infectious disease such as hepatitis C virus (HCV) is a global clinical issue because of its significant morbidity and mortality. Novel anti-hepatitis C drugs are continuously developed to decrease the pervasiveness of the infection around the world. A synthetic ravidasvir, benzimidazole-naphthylene-imidazole derivatives, has been used as an anti-HCV drug. In this study, the identification of ravidasvir’s metabolites and its pharmacokinetics in rats were determined using information-dependent acquisition (IDA) and multiple reaction monitoring (MRM) scanning modes in linear ion trap liquid chromatography tandem-mass (LC-MS/MS) instrument, respectively. Two time-programming linear-gradient chromatographic methods were employed using Kinetex® 2.6 μm C (50 × 3 mm) column and Luna® 3 μm HILIC column (100 × 4.6 mm) for the qualitative and quantitative determination of ravidasvir and its metabolites, respectively. In silico prediction where sites in a molecule are susceptible to metabolism by cytochrome P was implemented, which helped in proposing the metabolic pathway of ravidasvir. The most dominant metabolite in rat liver microsomal (RLM) samples was oxidative ravidasvir, where one O-demethylated metabolite and eight isomers of the oxidative ravidasvir metabolites were identified. The study provides essential data for proposing the metabolic pathway and successfully applied it to determine the pharmacokinetics of ravidasvir in rat plasma.
This article is protected by copyright. All rights reserved.