A fast, sensitive and greener stability-indicating HPLC method for the quantitative determination of osimertinib

Abstract A rapid, sensitive, and environmentally friendly reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the quantitative determination of osimertinib, a third-generation EGFR tyrosine kinase inhibitor, in pharmaceutical formulations. The method utilizes an isocratic mobile phase of acetonitrile and 0.1 M ammonium acetate (1:1, v/v), with chromatographic separation achieved on a C18 column and detection at 276 nm. Method validation demonstrated excellent linearity over the range of 2.40–20.29 μg mL −1 ( R 2 = 0.9988), high accuracy (mean recoveries 90–105%), and precision (RSD <1% intra-day, <2% inter-day). Robustness testing confirmed the method's resilience to minor operational changes, and sensitivity was reflected in low limits of detection (0.843 μg mL −1 ) and quantification (2.55 μg mL −1 ). Forced degradation studies revealed significant osimertinib instability under acidic, alkaline, and oxidative conditions, but relative stability under thermal stress, confirming the method's stability-indicating capability. Greenness assessment using the AGREE tool yielded a score of 0.82, reflecting strong adherence to green analytical chemistry principles. This validated method is suitable for routine quality control and stability studies of osimertinib, offering both analytical reliability and environmental sustainability.