Simultaneous determination of alflutinib and its active metabolite in human plasma using liquid chromatography-tandem mass spectrometry
文献类型：期刊论文
| 作者 | Liu, Xiaoyun1,2; Li, Wei2; Zhang, Yifan2 ; Jian, Yong3; Zhao, Qianyu3; Zhong, Dafang1,2
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| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
 |
| 出版日期 | 2019-11-30 |
| 卷号 | 176页码:6 |
| 关键词 | LC-MS/MS Alflutinib AST2818 Pharmacokinetics Human plasma |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2019.06.032 |
| 通讯作者 | Zhong, Dafang(dfzhong@simm.ac.cn) |
| 英文摘要 | Alflutinib, or known as AST2818, is an irreversible tyrosine kinase inhibitor that selectively inhibits EGFR mutations, especially T790M. At present, alflutinib has undergone phase II/III clinical trials for non-small cell lung cancer (NSCLC) treatment in China. The present study aimed to analye the pharmacokinetics of alflutinib and its active metabolite AST5902 in a plasma sample of NSCLC patient. A sensitive and highly selective method was optimized and validated for the detection of alflutinib and AST5902 using a liquid chromatography-tandem mass spectrometry. After precipitating proteins with acetonitrile, alflutinib, AST5902 and AST2818-d(3) (internal standard) were analyzed with a Waters BEH C-18 column. The mobile phase was optimized with acetonitrile: ammonium acetate (2 mmol/L) containing 0.2% formic acid using gradient elution. Separation was achieved within a total chromatographic running time of 2.1 min. Quantification was carried out using positive ion multiple reaction monitoring mode at ion transitions m/z 569.3 -> 441.2, 555.1 -> 498.2 and 572.3 -> 441.2 for alflutinib, AST5902 and AST2818-d(3), respectively. An excellent linearity was observed for alflutinib and AST5902 within concentration ranges of 0.20-100 and 0.050-25.0 ng-mL(-1), respectively. Notably, the lower limit of quantification for alflutinib and AST5902 were 0.20 and 0.050 ng/mL, respectively. The intra- and inter-day accuracy of alflutinib were 0.7-2.9%, while its intra- and inter-assay precision were <= 9.1% and <= 10.5%, respectively. The accuracy of AST5902 was within -0.2-3.9%, while the intra- and inter-assay precision were <= 8.0% and <= 8.6%, respectively. The recoveries of the analysts remained constant and could be reproduced at different concentrations. Furthermore, this analytical method could be applied to determine the pharmacokinetic analysis of alflutinib and AST5902 in human plasma. (C) 2019 Published by Elsevier B.V. |
| WOS关键词 | OSIMERTINIB ; INHIBITORS ; QUANTIFICATION ; OLMUTINIB ; ASSAY |
| 资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050306] ; National Natural Science Foundation of China[81521005] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000489000700010 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/282711]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhong, Dafang |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China 3.Shanghai Allist Pharmaceut Technol Co Ltd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Xiaoyun,Li, Wei,Zhang, Yifan,et al. Simultaneous determination of alflutinib and its active metabolite in human plasma using liquid chromatography-tandem mass spectrometry[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2019,176:6. |
| APA | Liu, Xiaoyun,Li, Wei,Zhang, Yifan,Jian, Yong,Zhao, Qianyu,&Zhong, Dafang.(2019).Simultaneous determination of alflutinib and its active metabolite in human plasma using liquid chromatography-tandem mass spectrometry.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,176,6. |
| MLA | Liu, Xiaoyun,et al."Simultaneous determination of alflutinib and its active metabolite in human plasma using liquid chromatography-tandem mass spectrometry".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 176(2019):6. |
入库方式： OAI收割
来源：上海药物研究所
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