2.5 PK assessment
Approximately 3 mL blood was collected into heparin lithium anticoagulant tubes, gently reversed, and mixed 6–10 times. The plasma concentration of famitinib and SHR116637 was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at the Frontage Holdings Corporation (Shanghai). The analytical method was developed and validated to meet the standard operating procedure established by the sponsor. Plasma samples were stored at ‑80°C, and the detection was completed within the storage time limit (long-term stability period was 160 days). The concentration range of calibration standards for famitinib and SHR116637 was both 0.05-100 ng/mL. In each analytical batch, the number of quality control samples (QC) accounts for more than 5% of the total number of samples, and at least two samples at each concentration level per time. For famitinib, the inter-run precision was 2.9–4.1%,while the inter-run accuracy ranged between 1.3-3.1%. For the metabolite SHR116637, the inter-run precision and accuracy were 1.6-3.4% and -2.7-1.1%, respectively.