Development and Validation of a Forced Degradation Study for Profiling Favipiravir Degradants by LC-MS

Background: A comprehensive stressed degradation study was conducted to investigate the stability of favipiravir under various conditions, including acid, base, photolytic, thermal, and oxidative degradation. Objective: The objective of the proposed study is to follow the guidelines outlined in ICH Q1A (R2) to ensure methodological rigor. LC-MS analysis was employed to characterise the degradants formed during these stress conditions. Method: A C18 column (250mm x 4.6ID, 5 micron) was used in conjunction with a mobile phase composed of mixture of Methanol: Water in the ratio of 60:40 at a flow rate of 0.8 ml/min. The analysis was performed by using a PDA detector at ambient temperature, with a retention time of 4.23 minutes for the drug. UV detection at 225nm was utilised for quantification purposes. Result: Favipiravir was subjected to acidic, basic, photolysis, photochemical, and thermal forced degradation conditions. The developed method was validated and found satisfactory in terms of linearity, precision, accuracy, limit of detection (LOD), and limit of quantitation (LOQ). The results of the study unequivocally demonstrated the formation of a significant quantity of a new compound under acid, base, photolytic, hydrogen peroxide oxidation and thermal stress conditions. LC-MS data further corroborated the presence of stressed impurities in favipiravir. Conclusion: This method has been successfully implemented in quality control laboratories to determine favipiravir along with its decomposition products.