DEVELOPMENT AND VALIDATION OF STABILITY INDICATING HPLC METHOD FOR THE DETERMINATION OF RELATED SUBSTANCES IN MOLNUPIRAVIR DRUG SUBSTANCE

Molnupiravir, the oral prodrug of the antiviral activity of the ribonucleotide Beta-D-N4-hydroxycytidine (NHC) against SARS-CoV-2, has been demonstrated. In both in vitro and select clinical trials (NIH 2023). The research indicates that Molnupiravir could potentially be efficacious in mitigating the risk of severe COVID-19 and mortality associated with the virus, particularly among certain subgroups, during the Omicron era and in real-world setting. RNA-dependent RNA-Polymerase (RdRp), an enzyme utilised by the coronavirus to transcribe and replicate its viral RNA genome, is the target of Molnupiravir. Idd-19312 describes Molnupiravir as an isopropyl ester prodrug that undergoes cleavage in plasma by esterases from the host into the β-D-N4-hydroxycytidine (NHC) active nucleoside analogue. Molnupiravir, a direct-acting agent administered orally, demonstrates efficacy in treating SARS-CoV-2 infection in animals. Furthermore, in COVID-19 patients undergoing short-course, five-day therapy3,4, Molnupiravir demonstrated a favourable safety and tolerability profile and was found to be highly efficacious at reducing the viral load in the nasopharynx5,6. The efficacy and safety of Molnupiravir as an antiviral therapy for mild to moderate COVID-19 infections with a high risk of progression have been validated by preclinical and clinical studies 7- 12. The present study reports a developing method for determining and validating the stability of Molnupiravir and its related compounds in different conditions and forced degradation methods using reverse-phase HPLC.