Simultaneous determination of flumatinib and its two major metabolites in plasma of chronic myelogenous leukemia patients by liquid chromatography-tandem mass spectrometry
文献类型：期刊论文
| 作者 | Yang, Yong; Liu, Ke; Zhong, Dafang ; Chen, Xiaoyan
|
| 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:25-30 |
| 关键词 | Flumatinib mesylate N-Demethylated flumatinib Amide hydrolysis product Liquid chromatography-tandem mass spectrometry Pharmacokinetics |
| ISSN号 | 1570-0232 |
| DOI | 10.1016/j.jchromb.2012.03.008 |
| 文献子类 | Article |
| 英文摘要 | Flumatinib is an antineoplastic tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukemia (CML). Its major metabolites in the circulation are N-desmethyl flumatinib (M1) and amide hydrolysis product (M3). To investigate the pharmacokinetics of flumatinib in CML patients, a simple, specific and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of flumatinib and its two major metabolites in patient plasma. After a simple, one-step protein precipitation with methanol, flumatinib, its two metabolites, and internal standard (HHGV-E) were separated on a C-18 column using an isocratic mobile phase of methanol:5 mM ammonium acetate:formic acid (60:40:0.4, v/v/v). A total chromatographic run time of 4.2 min was achieved. The detection was performed in multiple reaction monitoring mode, using the transitions of m/z 563 -> m/z 463 for flumatinib, m/z 549 -> ml/z 463 for M1, m/z 303 -> m/z 175 for M3, and m/z 529 -> m/z 429 for HHGV-E. The method was linear over the concentration ranges of 0.400-400 ng/mL for flumatinib, 0.100-100 ng/mL for M1, and 0.200-200 ng/mL for M3, using only 50 mu L of plasma. The Intra- and inter-day precisions were less than 8.5% for flumatinib, 9.8% for M1, and 10.6% for M3 in terms of the relative standard deviation. The accuracy was within +/- 2.2% for flumatinib, +/- 6.0% for M1, and +/- 9.9% for M3 in terms of relative error. The validated method was successfully applied to clinical pharmacokinetic studies of flumatinib mesylate in CML patients following oral administration at all dosage regimens. (C) 2012 Elsevier B.V. All rights reserved. |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000303628700004 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278093]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Chen, Xiaoyan |
| 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 | Yang, Yong,Liu, Ke,Zhong, Dafang,et al. Simultaneous determination of flumatinib and its two major metabolites in plasma of chronic myelogenous leukemia patients by liquid chromatography-tandem mass spectrometry[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2012,895:25-30. |
| APA | Yang, Yong,Liu, Ke,Zhong, Dafang,&Chen, Xiaoyan.(2012).Simultaneous determination of flumatinib and its two major metabolites in plasma of chronic myelogenous leukemia patients by liquid chromatography-tandem mass spectrometry.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,895,25-30. |
| MLA | Yang, Yong,et al."Simultaneous determination of flumatinib and its two major metabolites in plasma of chronic myelogenous leukemia patients by liquid chromatography-tandem mass spectrometry".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 895(2012):25-30. |
入库方式： OAI收割
来源：上海药物研究所
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