Articles Accepted

Development and Validation of a Novel Stability Indicating Reverse Phase High Performance Liquid Chromatographic Method for Related Substances and Assay Analysis of Molnupiravir Drug Substance and Drug Product.
by Dr. SHREERANG JOSHI, 18 Apr 2022
Co-Author(s): MANOJ A. MANGUKIYA,Pritam V. Bagwe,Aman A. Desai

Molnupiravir, an oral ribonucleoside analog with broad-spectrum antiviral activity, is an isopropyl ester prodrug of β-D-N4-Hydroxycytidine and targets RNA-dependent RNA-polymerase enzyme. It blocks the SARS-CoV-2 replication and is suggested as a candidate for the treatment of COVID-19. A simple, accurate, precise new stability-indicating high-performance liquid chromatographic (HPLC) method was developed to determine related substances and assay Molnupiravir. The separation between Molnupiravir, known associated substances, and degradation products was achieved by using Shim-pack GWS C18 (250 mm x 4.6 mm) 5 µm column utilizing a gradient elution technique with 0.05% formic acid in water as mobile phase A and acetonitrile as mobile phase B, at the detector wavelength 260 nm, column oven set to 30°C and flow rate set to 0.8 ml min-1. The method is validated according to the current International Council for Harmonisation requirements. The calibration plot gave a linear relationship (minimum correlation coefficient was 0.9998) for all known analytes over the concentration range from LOQ to 200% of the specification level. LOD and LOQ for all known analytes were found in 0.05-0.08 µg ml-1 and 0.12-0.20 µg ml-1, respectively. The recovery study determined the accuracy of the proposed method, and for all the known analytes, the mean recovery was found to be 97.79-102.44%. The repeatability study showed that the method is precise within the acceptable limits. The results of robustness and solution stability studies were within the acceptable limits. Molnupiravir was subjected to stress conditions of acid, base, oxidative, thermal, humidity, and photolytic degradation. Molnupiravir was found to degrade in acid, alkali, and oxidative conditions, stable in thermal, moisture, and photolytic degradation condition. The degradation products were well resolved from known analyte peaks. Tentative structures for major degradants were assigned based on m/z values from LC-MS analysis. The proposed method shows excellent linearity, accuracy, precision, specificity, robustness, LOD, LOQ, and system suitability results within the acceptance criteria. The method is simple, accurate, precise, and reproducible for routine purity analysis of drug samples.

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