Abstract

The stability and purity of pharmaceutical compounds are critical for ensuring drug efficacy and patient safety. Avapritinib, a tyrosine kinase inhibitor used to treat gastrointestinal stromal tumors and other cancers, requires a robust analytical method for its quantification and stability assessment. This study presents a validated stability-indicating high-performance liquid chromatography (HPLC) method for the separation, identification, and quantification of avapritinib and its impurities under various stress conditions. The method utilizes an X-Bridge C18 (250 mm × 4.6 mm, 5 μm) column with a mobile phase composed of acetonitrile and a methanol–phosphate buffer mixture (pH 3.6, 0.01M) in a 70:30 v/v ratio, employing a linear gradient elution at 0.9 mL/min with UV detection at 251 nm. The method exhibited high selectivity and resolution (Rs > 2), excellent linearity (r² > 0.999) within 25–150 μg/mL for avapritinib and 0.25–1.5 μg/mL for its impurities, and precision with RSD% below 2%. Recovery studies confirmed accuracy (99.58% for avapritinib, 99.72–100.17% for impurities). Forced degradation studies identified significant degradation under acidic and photolytic conditions, leading to the formation of distinct degradation products (ADP 1, ADP 2, PDP 1, PDP 2, and PDP 3). Structural elucidation via mass spectrometry revealed degradation pathways, with ADP products forming under acidic conditions and PDP products under photolytic stress. The developed method provides a reliable tool for avapritinib quantification and stability assessment, offering critical insights into its degradation behavior for improved therapeutic safety and efficacy.

Keywords: avapritinib, degradation products, mass spectrometry, fragmentation

Article language: En