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

Background BPI-43487 is a novel irreversible fibroblast growth factor receptor 4 inhibitor.Research design and methods 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.Results 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.Conclusions This method was further successfully applied to a pharmacokinetic study of BPI-43487 capsules in Chinese patients with advanced solid tumors.China drug trials http://www.chinadrugtrials.org.cn is CTR20210565).