title: Determination of a novel Aurora-A (AurA) kinase AKI603 by UPLC-MS/MS and its application to a bioavailability study in rat.
abstract: A simple, sensitive and accurate ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of AKI603 in rat plasma has been firstly developed and validated. After a simple liquid-liquid extraction (LLE) with ethyl acetate, the analytes were separated on C18 column (2.1×100mm, 1.9μm, Thermo) by gradient elution with mobile phase of water (A) (containing 5mM ammonium acetate and 0.1% formic acid) and methanol (B) with a flow rate of 0.3mLmin(-1) and then analyzed by mass spectrometry in the positive multiple reactions monitoring (MRM) mode. The mass transitions monitored were m/z 410.0→352.9, m/z 457.1→367.9 for AKI603 and internal standard (Ly-7z), respectively. The developed method was validated for specificity, linearity and lower limit of quantification, intra- and inter-day precision and accuracy, extraction recovery, matrix effect and stability whose values satisfied the acceptable limits. The calibration curves for AKI603 was linear in concentration ranges of 0.025-5000ngmL(-1). The method has been successfully used to the bioavailability study of AKI603 administered to rats intravenously (2.5mg/kg) or orally (25mg/kg). The oral bioavailability of AKI603 in rats was calculated as 28.7±9.7%.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou City, Guangdong Province 510006, China.
authors.forename: Lingjie
authors.initials: L
authors.lastname: Huang
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gou
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China.
authors.forename: Zhangwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China.
authors.forename: Jiangying
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou City, Guangdong Province 510006, China.
authors.forename: Dingsheng
authors.initials: D
authors.lastname: Wen
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China.
authors.forename: Fulin
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou City, Guangdong Province 510006, China.
authors.forename: Gui
authors.initials: G
authors.lastname: Lu
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China.
authors.forename: Huichang
authors.initials: H
authors.lastname: Bi
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: zhonggp@mail.sysu.edu.cn.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D011720:Pyrazoles / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D051381:Rats; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C000597114:AKI603; D011720:Pyrazoles; D011743:Pyrimidines
keywords: AKI603; Method validation; Oral bioavailability study; Rat; UPLC-MS/MS