Determination and Pharmacokinetic Study of Tandutinib in Rat Plasma by UPLC-MS/MS

A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination and pharmacokinetic invesligation of tandutinib in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2 mL of acetonitrile to a 0.1 mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile0.1% formic acid in water with gradient elution. The total run time was 4.0 min and the elution of tandutinib was at 1.65 min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring (MRM) mode using the respective transitions m/z 563.6 -> 126.2 for tandutinib and m/z 285.2 -> 193.1 for diazepam (internal standard), respectively. The calibration curve was linear over the range of 1-1000 ng/mL with a lower limit of quantitation (LLOQ) of 1.0 ng/mL. Mean recovery of tandutinib in plasma was in the range of 82.1-87.8%. Intra-day and inter-day precision were both < 113%. This method was successfully applied in pharmacokinetic study after oral administration of 50 mg/kg tandutinib in rats.