Determination of a novel Aurora-A (AurA) kinase AKI603 by UPLC-MS/MS and its application to a bioavailability study in rat.
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| 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%.
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| Authors | Zhenzhen Zhao, Lingjie Huang, Xiaoli Gou, Zhangwei Li, Jiangying Chen, Dingsheng Wen, Fulin Jiang, Gui Lu, Huichang Bi, Min Huang, Guoping Zhong |
| Journal | Journal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 125 Pg. 303-9 (Jun 05 2016) ISSN: 1873-264X [Electronic] England |
| PMID | 27070132 (Publication Type: Journal Article, Validation Study) |
| Copyright | Copyright © 2016 Elsevier B.V. All rights reserved. |
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