Development of Stability Indicating HPLC-UV Method for Determination of Process Impurities and Degradation Products in Sofosbuvir and Velpatasvir Tablets

Abstract

A simple and sensitive stability indicating HPLC-UV method was developed for the analysis of process impurities and degradation products in Sofosbuvir and Velpatasvir pharmaceutical formulations. Analysis was performed on C18 analytical column (250 mm 4.6 mm, 5 m), using a mobile phase of 0.05M ammonium acetate buffer (pH 6.5) with acetonitrile at 45 : 55 (v/v) ratio and a flow rate of 1.0 mL/min. The detection wavelength for simultaneous determination of both ingredients using UV detector was 268 nm. The method was validated for accuracy, precision, linearity, and specificity using reference standards of process impurities and degradation products. The calibration curve was linear and the limits of detection and quantification were determined using 3 /slope and 10 /slope expressions, respectively. Forced degradation studies for Sofosbuvir and Velpatasvir drug substances and products were designed under different environmental stress conditions. The effect of alkaline, acidic, oxidative, and thermal stress conditions on Sofosbuvir and Velpatasvir substances and dosage forms was studied. The influence of heat and humidity was studied at 80 5°C and 75 5% RH. Similarly, the photolytic studies were performed on visible light at 200 W h/m 2 UV and 1.2 million lux h/m 2 in a climatic chamber. The proposed method is stability-indicating and has been successfully applied to the analysis of process impurities and degradation products in Sofosbuvir and Velpatasvir pharmaceutical formulations. The degradation products were characterized by MS, NMR and IR spectroscopy analysis for identification of degradation products and determination of mechanisms.

Forced Degradation Studies and Development and Validation of HPLC-UV Method for the Analysis of Velpatasvir Copovidone Solid Dispersion

“…The official pharmacopeial monograph is also not available for the analysis of drug substance and pharmaceutical formulations. Very few analytical methods, focusing on simultaneous analysis of VEL and Sofosbuvir combined formulation, are reported in literature [ 13 , 14 , 15 , 16 , 17 , 18 ] Stability indicating methods for the analysis of VEL pure drug substance and degradation studies are also reported [ 19 , 20 , 21 , 22 , 23 ] but have limited information and discrepancies with published literature of FDA and MHRA [ 24 , 25 ]. As per MHRA public assessment report, VEL is photolabile, however it is reported stable in forced degradation studies published on UPLC [ 26 ].…”