Forced degradation study of daclatasvir, darunavir, favipiravir and remdesivir
摘要
A forced degradation study was performed on four antivirals—daclatasvir, darunavir, favipiravir, and remdesivir. The study exposed the antivirals to pH-neutral media at three temperatures (25 °C, 30 °C, and 40 °C), to an acidic solution (1 M HCl at 25 °C), to an alkaline solution (1 M NaOH at 25 °C), and to a 30% H2O2 solution as a strong oxidizing agent (also at 25 °C). Liquid chromatography methods were developed and validated for each antiviral to monitor their concentrations during the study. In this study, we analyzed the levels of the antivirals under specific stress conditions as indicators of their persistence in the environment. The focus of this study was on evaluating the susceptibility of the selected antivirals to degradation, which was ranked from least to greatest under various stress conditions. The identification and characterization of degradation products were not addressed in this work, as a comprehensive investigation of these aspects will be presented in a subsequent study. For hydrolysis in a pH-neutral medium, the order was: remdesivir, favipiravir, daclatasvir, darunavir. In an acidic medium, the order was: favipiravir, daclatasvir, remdesivir, darunavir. In an alkaline medium, the order was: favipiravir, daclatasvir, darunavir, remdesivir. For oxidative degradation, the order was: darunavir, favipiravir, remdesivir, daclatasvir. Higher temperatures increased degradation of the antivirals.