Direct quantification of anorethidrani disuccinate and determination of sterol metabolites by chemical derivatization combined with LC-MS/MS: Application to a Phase I pharmacokinetic study in humans
文献类型：期刊论文
| 作者 | Jiang, Jinfang; Li, Liang ; Lu, Youming; Chen, Yunhui; Chen, Xiaoyan; Zhong, Dafang
|
| 刊名 | JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
 |
| 出版日期 | 2020-11-10 |
| 卷号 | 1157页码:9 |
| 关键词 | Anorethidrani disuccinate ACP Sterol metabolite Glycidyl trimethyl ammonium chloride LC-MS/MS |
| ISSN号 | 1570-0232 |
| DOI | 10.1016/j.jchromb.2020.122290 |
| 通讯作者 | Zhong, Dafang(dfzhong@simm.ac.cn) |
| 英文摘要 | Anorethidrani disuccinate (ACP) is a domestically designed A-decarbonized steroid that is currently being investigated in Phase I clinical trials for the treatment of solid tumors. Only the parent drug exhibited antitumor activity; its sterol metabolite M2 showed obvious antiestrogenic effects. We have developed a rapid, sensitive, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the direct quantification of ACP and a chemical derivatization method that can be used to quantify M2 derivatized with glycidyl trimethyl ammonium chloride (GTMA). A simple protein precipitation procedure was performed to quantify ACP. Injections were obtained within 3.5 min on an Eclipse Plus Phenyl-Hexyl column (50 mm x 2.1 mm i.d., 1.8 mu m) with gradient elution; the calibration curve was linear over the range of 2.00-8000 ng/mL. For quantification of M2 in plasma, analytes were extracted by protein precipitation and converted to their GTMA derivatives at 60 degrees C for 2 h at pH 12; the analytes and coelutants were separated on a Luna C8(2) column (50 mm x 2.0 mm i.d., 5.0 mu m). The precision (RSD) and accuracy (RE) of the infra- and interday determinations were within 10%. The derivatization procedure is a novel method for sterol determination by LC-MS/MS. The results confirmed the usefulness of this method for characterizing the pharmacokinetic profiles of ACP and its major metabolite M2 in a Phase I pharmacokinetic study. |
| WOS关键词 | AROMATASE INHIBITOR ; BIOANALYSIS ; VALIDATION ; SULFATASE ; ESTRONE ; ASSAY |
| 资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050306] ; National Natural Science Foundation of China[81521005] ; National Natural Science Foundation of China[81703602] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000580580600005 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/291526]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhong, Dafang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201210, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Jinfang,Li, Liang,Lu, Youming,et al. Direct quantification of anorethidrani disuccinate and determination of sterol metabolites by chemical derivatization combined with LC-MS/MS: Application to a Phase I pharmacokinetic study in humans[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2020,1157:9. |
| APA | Jiang, Jinfang,Li, Liang,Lu, Youming,Chen, Yunhui,Chen, Xiaoyan,&Zhong, Dafang.(2020).Direct quantification of anorethidrani disuccinate and determination of sterol metabolites by chemical derivatization combined with LC-MS/MS: Application to a Phase I pharmacokinetic study in humans.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,1157,9. |
| MLA | Jiang, Jinfang,et al."Direct quantification of anorethidrani disuccinate and determination of sterol metabolites by chemical derivatization combined with LC-MS/MS: Application to a Phase I pharmacokinetic study in humans".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 1157(2020):9. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。