A sensitive LC-MS/MS method for simultaneous determination of cabozantinib and its metabolite cabozantinib N-oxide in rat plasma and its application in a pharmacokinetic study
文献类型：期刊论文
| 作者 | Ren, Lian-jie2,6; Wu, Hua-jing3,4; Sun, Li-han3; Xu, Xue3; Mo, Li-ying1; Zhang, Lei5; Zhang, Jun-ying1; Wu, Chun-yong3 |
| 刊名 | BIOMEDICAL CHROMATOGRAPHY
 |
| 出版日期 | 2018-07 |
| 卷号 | 32期号:7 |
| 关键词 | cabozantinib cabozantinib N-oxide LC-MS MS pharmacokinetics plasma |
| ISSN号 | 0269-3879 |
| DOI | 10.1002/bmc.4227 |
| 文献子类 | Article |
| 英文摘要 | Cabozantinib (CBZ) is used for the treatment of progressive, metastatic medullary thyroid cancer. Its major oxidative metabolite is cabozantinib N-oxide (CBN), which contains a structural alert associated with mutagenicity, yet the pharmacokinetics studies lack the simultaneous investigation of CBN and dose proportionality. In the current study a simple LC-MS/MS method was developed and validated for the simultaneous estimation and pharmacokinetic investigation of CBZ and CBN in rat plasma. The analytes were separated on a Waters Atlantics C-18 column (2.1 x 150mm, 3 m). The mass spectrometry analysis was conducted in positive ionization mode with multiple reaction monitoring. Good linearity was observed over the concentration ranges of 0.500-5000ng/mL for CBZ and 0.525-2100ng/mL for CBN. The extraction recoveries were constant and the intra- and inter-batch precision and accuracy were acceptable for the analysis of biological samples. The method was successfully applied for the simultaneous estimation of CBZ and CBN in a pharmacokinetic study in Sprague-Dawley rats. After oral administration of CBZ (1, 5 and 12.6mg/kg), although CBZ showed dose proportionality, the metabolite CBN showed obvious nonlinear elimination pharmacokinetics with greater than dose-proportional increases in exposure. |
| WOS关键词 | RENAL-CELL CARCINOMA ; DOSE PROPORTIONALITY ; OPEN-LABEL ; VOLUNTEERS ; EVEROLIMUS |
| 资助项目 | Natural Science Foundation of Jiangsu Province[BK2012358] ; Specialized Research Fund for the Doctoral Program of Higher Education[20120096120004] ; National Natural Science Foundation of China[81673681] ; National Natural Science Foundation of China[81473357] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000434409100014 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279691]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Zhang, Jun-ying; Wu, Chun-yong |
| 作者单位 | 1.China Pharmaceut Univ, Dept Pharmaceut Tradit Chinese Med, Nanjing, Jiangsu, Peoples R China; 2.China Food & Drug Adm, Ctr Drug Evaluat, Beijing, Peoples R China; 3.China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing, Jiangsu, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Ctr Drug Safety Evaluat & Res, Shanghai, Peoples R China; 5.Shandong Inst Food & Drug Control, Dept Chem Drug Div, Jinan, Shandong, Peoples R China 6.China Pharmaceut Univ, Sch Pharm, Dept Pharmaceut, Nanjing, Jiangsu, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Ren, Lian-jie,Wu, Hua-jing,Sun, Li-han,et al. A sensitive LC-MS/MS method for simultaneous determination of cabozantinib and its metabolite cabozantinib N-oxide in rat plasma and its application in a pharmacokinetic study[J]. BIOMEDICAL CHROMATOGRAPHY,2018,32(7). |
| APA | Ren, Lian-jie.,Wu, Hua-jing.,Sun, Li-han.,Xu, Xue.,Mo, Li-ying.,...&Wu, Chun-yong.(2018).A sensitive LC-MS/MS method for simultaneous determination of cabozantinib and its metabolite cabozantinib N-oxide in rat plasma and its application in a pharmacokinetic study.BIOMEDICAL CHROMATOGRAPHY,32(7). |
| MLA | Ren, Lian-jie,et al."A sensitive LC-MS/MS method for simultaneous determination of cabozantinib and its metabolite cabozantinib N-oxide in rat plasma and its application in a pharmacokinetic study".BIOMEDICAL CHROMATOGRAPHY 32.7(2018). |
入库方式： OAI收割
来源：上海药物研究所
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