Development of a Sensitive and Rapid UPLC-MS/MS Method for the Determination of Apatinib in Rat Plasma: Application to a Pharmacokinetic Study

An accurate and validated liquid chromatography method with triple quadrupole mass spectrometry has been developed for the determination of apatinib in rat plasma. Plasma samples were prepared by precipitating protein with acetonitrile. The analytes were separated by a reversed-phase BEH C18 column (2.1 x 50 mm, 1.7 mu m, Waters, USA) maintained at 40 degrees C. The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with a gradient elution pumped at a flow rate of 0.4 mL/min. The analytes were detected with positive electrospray ionization in multiple reaction monitoring (MRM) mode for target fragment ions m/z 398.1 -> 212.0 for apatinib and m/z 494.2 -> 394.1 for imatinib (IS). Good linearity was achieved to quantify the concentration ranges of 5-500 ng/mL for apatinib with a lower limit of quantification (LLOQ) of 1 ng/mL. The mean recovery of apatinib from plasma exceeded 71.37%. The intra- and inter-assay precisions were both less than 7.98%. This method was successfully applied to a pharmacokinetic study of apatinib after a intragastric administration of 10, 40, and 100 mg/kg in rats.