An LC-MS/MS method for the quantitation of cabozantinib in rat plasma: Application to a pharmacokinetic study

A simple, rapid and sensitive high-performance liquid chromatography tandem mass-spectrometric method (LC-MS/MS) for the novel multiple tyrosine kinase inhibitor (TKI) cabozantinib was developed and validated using erlotinib as internal standard (IS). Plasma samples were pre-treated by liquid liquid extraction with ethyl acetate. Separation was achieved on a reversed phase C18 column (50 x 2 mm, 5 mu m) at ambient temperature using isocratic elution with acetonitrile-water (45:55, v/v) containing 5 mM ammonium formate buffer (finally adjusted to apparent pH* = 5.0 with formic acid) at a flow rate of 0.4 mL/min.The analytes were monitored by a triple quadrupole tandem mass spectrometer with electrospray ionization source in the positive ion mode. Calibration curve was linear (r>0.99) in a concentration range of 0.5-1000 ng/mL with the lower limit of quantification (LLOQ) of 0.5 ng/mL. Intra- and inter-day accuracy and precision were validated by relative error values (RE) and relative standard deviation values (RED), respectively, which were both lower than the limit of 15%. This method was successfully applied to a pharmacokinetic study of cabozantinib in rats. (C) 2015 Elsevier B.V. All rights reserved.Biochemical Research MethodsChemistry, AnalyticalSCI(E)EIPubMed1ARTICLEluwei_pk@bjmu.edu.cn; liliang@hsc.pku.edu.cn119-12398