A Stability-Indicating HPLC Method for Favipiravir and its Related Substances

Background and Aims: This study aimed to improve an HPLC method for the quantification of favipiravir (FVP) and its impurities and apply it to a marketed pharmaceutical product. Methods: Chromatographic separations were achieved on a C18 column. The mobile phase comprised 10 mM potassium dihydrogen phosphate buffer (pH 4.0):acetonitrile (90:10 v/v) and acetonitrile in the gradient mode. The peaks were detected at 238 nm and the flow rate was set at 1.5 mL/min. The optimised method has been validated as per the International Conference on Harmonisation (ICH) guidelines Q2 (R1). A sharp peak of FVP was obtained at 5.5 min with no interfering peaks. In addition, the degradation study was conducted under acidic, basic, oxidative, photolytic, and thermal stress conditions. Results: In the calibration curve experiments, the linearity was between 0.5 – 3 μg/mL and r2=0.9985. Recovery ranging from 97.5% to 102.2% for the drug and impurities. The limit of detection (LOD) and limit of quantification (LOQ) concentrations of FVP and its impurities were 0.07 μg/mL and 0.2 μg/mL using s/ n:3, respectively. The precision studies were carried out and the relative standard deviation (RSD) values were found to be between 1.01 and 1.65% and 0.67-1.75% for intra-day precision and inter-day precision; respectively. No degradation peak appeared in the acidic hydrolysis, base hydrolysis, and photolysis stress studies. When the drug was subjected to thermal degradation, impurity B was observed. The degradation of the drug substances was obtained at 0.67% and 1.87% by thermal degradation and oxidation; respectively. Conclusion: The stability-indicating chromatographic methods for the determination of FVP and related components were developed and applied in tablets.