UHPLC-MS/MS method to determine FP-208 in human plasma and its application to a pharmacokinetic study.

FP-208 is a novel and effective small-molecule inhibitor blocking the mammalian target of rapamycin complex-1/mammalian target of rapamycin complex-2/PI3Ka. To investigate the pharmacokinetic profile of FP-208, a rapid and reliable analytical method was needed to be established to determine FP-208 in the plasma of patients with solid tumors. FP208 was separated on a charged surface hybrid (CSH) C18 column (2.1 mm × 50 mm, 1.7 μm) after the plasma samples were purified using a protein precipitation method. Detection was performed on an AB Sciex 5500 mass spectrometer in the positive electrospray ionization mode. The established method was validated according to the bioanalytical guidelines. For the first time, the developed and validated method was successfully applied in the first-in-human study for FP-208 in patients with solid tumors after oral administration (Number: CTR20180683).