A validated UHPLC-MS/MS method for determination of BPI-43487 and its metabolite BPI-43739 in human plasma and its application to a pharmacokinetic study in Chinese patients with advanced solid tumors

BPI-43487 is a novel irreversible fibroblast growth factor receptor 4 inhibitor. A simple and reliable liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of BPI-43487 and its active metabolite BPI-43739 in human plasma. BPI-43487B was used as the internal standards (IS). Plasma samples were protein precipitated by acetonitrile and processed samples were chromatographed on an AQUITY UHPLC BEH C18 column (50 × 2.1 mm, i.d. 1.7 μm) with acetonitrile and 10 mM ammonium acetate containing 0.1% formic acid (v/v) as the mobile phase. Calibration curves demonstrated good linearity (R ≥0.99) over the concentration range of 10.0–5000 ng/mL for both analytes. Intra- and inter-batch precisions were ≤9.2% for BPI-43487 and ≤8.7% for BPI-43739. The accuracies were 94.6–104.8% for BPI-43487 and 95.0–108.4% for BPI-43739. This method was further successfully applied to a pharmacokinetic study of BPI-43487 capsules in Chinese patients with advanced solid tumors. http://www.chinadrugtrials.org.cn is CTR20210565). This research focused on a new liver cancer drug called BPI-43487, and the substance it produces in the body, BPI-43739. To do this, we developed a new method to measure levels of these two substances in plasma. We prepared plasma samples using organic solvents and then used precise laboratory instruments to measure the drug amounts. This method proved to be reliable and consistent. It was successfully used in a clinical study with Chinese cancer patients, helping scientists understand how the drug behaves in the body after taking the BPI-43487 capsule, which is a crucial step in developing new treatments.