title: Quantification and pharmacokinetics of crizotinib in rats by liquid chromatography-tandem mass spectrometry.
abstract: Crizotinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and can be used to treat ALK-positive nonsmall-cell lung cancer. A rapid and simple high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of crizotinib in rat plasma using a chemical synthetic compound buspirone as the internal standard (IS). The plasma samples were pretreated by a simple protein precipitation with methanol-acetonitrile (1:1, v/v). Chromatographic separation was successfully achieved on an Agilent Zorbax XDB C18 column (2.1 × 50 mm, 3.5 µm). The gradient elution system was composed of 0.1% formic acid aqueous solution and 0.1% formic acid in methanol solution. The flow rate was set at 0.50 mL/min. The multiple reaction monitoring was based on the transitions of m/z = 450.3 → 177.1 for crizotinib and 386.2 → 122.2 for buspirone (IS). The assay was successfully validated to demonstrate the selectivity, matrix effect, linearity, lower limit of quantification, accuracy, precision, recovery and stability according to the international guidelines. The lower limit of quantification was 1.00 ng/mL in 50 μL of rat plasma. This LC-MS/MS assay was successfully applied to the quantification and pharmacokinetic study of crizotinib in rats after intravenous and oral administration of crizotinib. The oral absolute bioavailability of crizotinib in rats was 68.6 ± 9.63%. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Cancer and Metastasis Research, Capital Medical University, Beijing, 100069, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Beijing Cancer Hospital and Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Cancer and Metastasis Research, Capital Medical University, Beijing, 100069, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D000077547:Crizotinib; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics*; D011720:Pyrazoles / Q000493:pharmacokinetics*; D011725:Pyridines / Q000493:pharmacokinetics*; D011786:Quality Control; D051381:Rats; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib
keywords: LC-ESI-MS/MS; crizotinib; pharmacokinetics; rat