Sabiha Kamal, Mohammad Abdullah Taher, Md. Moniruzzaman, Rickta Rani Das and Mala Khan^*,

Bangladesh Reference Institute for Chemical Measurements (BRiCM), Dr. Qudrat-e-Khuda Road, Dhanmondi, Dhaka-1205, Bangladesh

*Corresponding author: E-mail: bricmdg@yahoo.com

Molnupiravir, an orally active RdRp inhibitor, though originally developed to use against influenza, has become a promising therapeutic candidate for COVID-19 infection by acting as prodrug of the nucleoside analog β-d-N4-hydroxycytidine (NHC or EIDD-1931) in the isopropyl ester form. Accordingly, it has been approved by MHRA, UK in November 2021 to use against COVID-19. This work presents the development and validation of a high-performance liquid chromatography (HPLC) method for the rapid and accurate assessment of molnupiravir. The objective of this approach is to ensure the quality control of Lagevrio^® capsules and their generic versions available in Bangladesh. The separation was carried out by isocratic elution through C18 column (4.6 mm × 250 mm i.d., 5 μ particle size) at 40 °C temperature at a constant flow rate of 1.0 mL/min using acetonitrile and 1% orthophosphoric acid as buffer (20:80, v/v). A 10 μL sample was injected and elution was monitored at 210 nm wavelength. The calibration curve over the concentration range of 80-120% were found to be linear (r² = 0.9998), the %RSD for intra-day (0.31%) and inter-day (0.73%) precision indicate good precision where %recovery was found in the acceptable range of 99.9-100.4% as per ICH guidelines. The method was successfully applied to commercial pharmaceuticals, Lagevrio^® and its generic versions and and the results were found to be consistent with the label claims (95-105%).

Molnupiravir, Prodrug, SARS-CoV-2, HPLC, MHRA.