Development and validation of a sensitive LC-MS/MS assay for the simultaneous quantification of allitinib and its two metabolites in human plasma
文献类型：期刊论文
| 作者 | Lin, Lishan; Gao, Zhiwei ; Chen, Xiaoyan; Zhong, Dafang
|
| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
 |
| 出版日期 | 2013-12 |
| 卷号 | 86页码:49-55 |
| 关键词 | Liquid chromatography-tandem mass spectrometry Allitinib Metabolite Pharmacokinetics Human plasma |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2013.07.003 |
| 文献子类 | Article |
| 英文摘要 | Allitinib, also known as AST1306, is a novel irreversible inhibitor of the epidermal growth factor receptors 1 and 2. Allitinib is currently used in clinical trial to treat solid tumors. A previous study showed that allitinib is extensively metabolized in humans. Amide hydrolysis metabolite (M6) and 29,30-dihydrodiol allitinib (M10) are the major metabolites in circulation. To study the pharmacokinetics of allitinib and its two major metabolites in cancer patients, a rapid, sensitive and reliable LC-MS/MS method was developed and validated for the simultaneous determination of allitinib, M6 and M10 in human plasma. After simple protein precipitation, the analytes and the combined internal standards (lapatinib and NB-2, an analog of allitinib) were separated on a Zorbax Eclipase XDB C-18 column (50 mm x 4.6 mm, 1.8 mu m, Agilent) using a mobile phase of 5 mM ammonium acetate with 0.1% formic acid (phase A) and 50% (v/v) methanol in acetonitrile (phase B) with gradient elution. Mass spectrometric detection was conducted by atmospheric-pressure chemical ionization in positive ion multiple reaction monitoring modes using AB Sciex Triple Quad 6500 system. Linear calibration curves were obtained for the following concentration range: 0.300-200 ng/ml for allitinib; 0.030-20.0 ng/ml for M6; and 0.075-50.0 ng/ml for M10. Intra-day and inter-day accuracy and precision were within the acceptable limits of +/- 15% at all of the concentrations. The method was successfully applied to a preliminary clinical pharmacokinetic study following oral administration of allitinib tosylate tablets in cancer patients. (C) 2013 Elsevier B.V. All rights reserved. |
| WOS关键词 | PHARMACOKINETICS ; FOOD |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000325671200005 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277368]  |
| 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, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin, Lishan,Gao, Zhiwei,Chen, Xiaoyan,et al. Development and validation of a sensitive LC-MS/MS assay for the simultaneous quantification of allitinib and its two metabolites in human plasma[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2013,86:49-55. |
| APA | Lin, Lishan,Gao, Zhiwei,Chen, Xiaoyan,&Zhong, Dafang.(2013).Development and validation of a sensitive LC-MS/MS assay for the simultaneous quantification of allitinib and its two metabolites in human plasma.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,86,49-55. |
| MLA | Lin, Lishan,et al."Development and validation of a sensitive LC-MS/MS assay for the simultaneous quantification of allitinib and its two metabolites in human plasma".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 86(2013):49-55. |
入库方式： OAI收割
来源：上海药物研究所
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