LAUSR

Abstract Drug substances undergo degradation during manufacturing process and storage of finished pharmaceutical products which often results in the generation of degradation products. When process-related substances and degradation products are present as impurities, the therapeutic effect of the drug may alter or cause adverse effects. To address these issues, a mass compatible selective reverse phase UPLC method was developed and validated for separation of Velpatasvir (VPR) and some of its impurities. VPR was subjected to hydrolytic, oxidative, photolytic and thermal stress conditions as prescribed by ICH. Four process-related substances and eight stress degradation products (DPs) were separated on an Acquity Phenyl-Hexyl (100 × 2.1 mm x 1.8 µm) column using 0.1% formic acid and methanol as eluent with gradient program. The same method was applied to LC coupled tandem mass spectrometer for separation and structure elucidation of impurities. Out of eight degradation impurities; two degradation products (V1 and V2) were obtained in acid hydrolysis, another two DPs (V3 and V4) formed in alkaline hydrolysis. Four DPs (V5, V6, V7 and V8) were obtained in oxidative stress. V7 and V8 were obtained as major degradation products and their chemical structures were further confirmed by NMR experiments. The performance of this method was validated for parameters by following ICH Q2 (R1) guideline. This method can be utilized in the identification of impurities in bulk drug manufacturing and dosage form design studies.