Quantitative analysis of tivantinib in rat plasma using ultra performance liquid chromatography with tandem mass spectrometry.

Abstract In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for the quantitative determination of tivantinib in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 (2.1 mm × 50 mm, 1.7 μm) column with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 1.0–100 ng/mL ( r 2  > 0.9967) with a lower limit of quantification (1.0 ng/mL). The extraction recovery was in the range of 79.4–84.2% for tivantinib and 80.3% for carbamazepine (internal standard, IS). The intra- and inter-day precision was below 8.9% and accuracy was from −7.2% to 9.5%. No notable matrix effect and astaticism was observed for tivantinib. The method has been successfully applied to a pharmacokinetic study of tivantinib in rats for the first time, which provides the basis for the further development and application of tivantinib.