title: An LC-MS/MS method for the quantitation of cabozantinib in rat plasma: application to a pharmacokinetic study.
abstract: 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 (50×2mm, 5μm) at ambient temperature using isocratic elution with acetonitrile-water (45:55, v/v) containing 5mM ammonium formate buffer (finally adjusted to apparent pH*=5.0 with formic acid) at a flow rate of 0.4mL/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 0.5-1000ng/mL with the lower limit of quantification (LLOQ) of 0.5ng/mL. Intra- and inter-day accuracy and precision were validated by relative error values (RE) and relative standard deviation values (RSD), respectively, which were both lower than the limit of 15%. This method was successfully applied to a pharmacokinetic study of cabozantinib in rats.
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Qinghong
authors: Q
authors: Su
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Jian
authors: J
authors: Li
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Xiwei
authors: X
authors: Ji
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Jingyun
authors: J
authors: Li
authors: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Tianyan
authors: T
authors: Zhou
authors: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: luwei_pk@bjmu.edu.cn.
authors: Wei
authors: W
authors: Lu
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: liliang@hsc.pku.edu.cn.
authors: Liang
authors: L
authors: Li
mesh_terms: D000813:Anilides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D011725:Pyridines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000813:Anilides; D011725:Pyridines; C558660:cabozantinib
keywords: Cabozantinib; LC-MS/MS; Pharmacokinetics; Rat plasma