Zhao Zhenzhen, Huang Lingjie, Gou Xiaoli, Li Zhangwei, Chen Jiangying, Wen Dingsheng, Jiang Fulin, Lu Gui, Bi Huichang, Huang Min, Zhong Guoping
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.
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou City, Guangdong Province 510006, China.
J Pharm Biomed Anal. 2016 Jun 5;125:303-9. doi: 10.1016/j.jpba.2016.03.041. Epub 2016 Mar 22.
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%.
