Analytical Quality by Design‐Based Stability‐Indicating UHPLC Method for Determination of Inavolisib in Bulk and Formulation

ABSTRACT Inavolisib is a novel, potent, and selective phosphatidylinositol‐3‐kinase alpha inhibitor recently approved for the treatment of phosphatidylinositol‐3‐kinase alpha‐mutated breast cancer. This research focuses on the UHPLC method development and method validation of a stability‐indicating RP‐UHPLC method for the quantification of inavolisib in bulk and pharmaceutical dosage forms. A specific and robust analytical method was developed using a shield RP18 column (50 mm × 1.0 mm, 1.7 µm) with isocratic elution comprising 0.1% trifluoroacetic acid and acetonitrile (60:40, v/v) at a flow rate of 0.5 mL/min. The injection volume was 5 µL, and detection was carried out at 257 nm using a UV detector. The total run time was 3.0 min. The method validation was carried out in compliance with ICH guidelines and demonstrated acceptable specificity, precision (%RSD < 1%), linearity ( r 2 = 0.9998), accuracy (99.5%–100.4% recovery), sensitivity (LOD: 1.0 µg/mL; LOQ: 3.0 µg/mL), and robustness. To assess the method's specificity, forced degradation studies carried out under different stress conditions, such as acidic, basic, oxidative, thermal, photolytic, and neutral conditions, confirmed the method's ability to selectively quantify inavolisib in the presence of degradation products. Mass balance values exceeded 95% in all the degradation conditions, and peak purity tests passed under all stress conditions. The robustness of the method was assessed using an analytical quality by design approach by introducing deliberate variations in critical parameters, including the flow rate of the mobile phase, the organic ratio of the mobile phase, and the column temperature. Therefore, this developed method, with a short run time of 3 min, is reliable and suitable for routine quality control and stability testing of inavolisib in pharmaceutical research and development and quality control departments.