Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study
文献类型：期刊论文
| 作者 | Ding, Juefang; Chen, Xiaoyan ; Dai, Xiaojian; Zhong, Dafang
|
| 刊名 | JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
 |
| 出版日期 | 2012-05-01 |
| 卷号 | 895页码:108-115 |
| 关键词 | Apatinib YN968D1 Metabolite Liquid chromatography-tandem mass spectrometry Pharmacokinetics Human plasma |
| ISSN号 | 1570-0232 |
| DOI | 10.1016/j.jchromb.2012.03.027 |
| 文献子类 | Article |
| 英文摘要 | Apatinib, also known as YN968D1, is a novel antiangiogenic agent that selectively inhibits vascular endothelial growth factor receptor-2. Currently, apatinib is undergoing phase II/III clinical trials in China for the treatment of solid tumors. Apatinib is extensively metabolized in humans, and its major metabolites in circulation include cis-3-hydroxy-apatinib (M1-1), trans-3-hydroxy-apatinib (M1-2), apatinib-25-N-oxide (M1-6), and cis-3-hydroxy-apatinib-O-glucuronide (M9-2). To investigate the pharmacokinetics of apatinib and its four major metabolites in patients with advanced colorectal cancer, a sensitive and selective liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of apatinib, M1-1, M1-2, M1-6, and M9-2 in human plasma. After a simple protein precipitation using acetonitrile as the precipitation solvent, all the analytes and the internal standard vatalanib were separated on a Zorbax Eclipse XDB C-18 column (50 mm x 4.6 mm, 1.8 mu m, Agilent) using acetonitrile: 5 mmol/L ammonium acetate with 0.1% formic acid as the mobile phase with gradient elution. A chromatographic total run time of 9 min was achieved. Mass spectrometry detection was conducted through electrospray ionization in positive ion multiple reaction monitoring modes. The method was linear over the concentration range of 3.00-2000 ng/mL for each analyte. The lower limit of quantification for each analyte was 3.00 ng/mL. The intra-assay precision for all the analytes was less than 11.3%, the inter-assay precision was less than 13.8%, and the accuracy was between -5.8% and 3.3%. The validated method was successfully applied to a clinical pharmacokinetic study following oral administration of 500 mg apatinib mesylate in patients with advanced colorectal cancer. (C) 2012 Elsevier B.V. All rights reserved. |
| WOS关键词 | INHIBITOR ; YN968D1 |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000303628700016 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278094]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Zhong, Dafang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Metab & Pharmacokinet, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ding, Juefang,Chen, Xiaoyan,Dai, Xiaojian,et al. Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2012,895:108-115. |
| APA | Ding, Juefang,Chen, Xiaoyan,Dai, Xiaojian,&Zhong, Dafang.(2012).Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,895,108-115. |
| MLA | Ding, Juefang,et al."Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 895(2012):108-115. |
入库方式： OAI收割
来源：上海药物研究所
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