Assay development for determination of DZ2002, a new reversible SAHH inhibitor, and its acid metabolite DZA in blood and application to rat pharmacokinetic study
文献类型：期刊论文
| 作者 | Jia, Weiwei1; Li, Jing1,2 ; Du, Feifei1; Sun, Yan3; Xu, Fang1; Wang, Fengqing1; Olaleye, Olajide E.1; Chen, Danghui1,4; Tang, Wei1; Zuo, Jianping1
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| 刊名 | JOURNAL OF PHARMACEUTICAL ANALYSIS
 |
| 出版日期 | 2019-02-01 |
| 卷号 | 9期号:1页码:25-33 |
| 关键词 | S-adenosyl-L-homocysteine hydrolase DZ2002 Carboxylesterases Pharmacokinetics |
| ISSN号 | 2095-1779 |
| DOI | 10.1016/j.jpha.2018.09.001 |
| 通讯作者 | Li, Chuan(chli@simm.ac.cn) |
| 英文摘要 | Methyl (S)-4-(6-amino-9H-purin-9-yl)-2-hydroxybutanoate (DZ2002) is a potent reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH). Due to its ester structure, DZ2002 is rapidly hydrolyzed in rat blood to 4-(6-amino-9H-purin-9-yl)-2-hydroxybutyric acid (DZA) during and after blood sampling from rats; this hampers accurate determination of the circulating DZ2002 and its acid metabolite DZA in rats. To this end, a method for determining the blood concentrations of DZ2002 and DZA in rats was developed by using methanol to immediately deactivate blood carboxylesterases during sampling. The newly developed bioanalytical assay possessed favorable accuracy and precision with lower limit of quantification of 31 nM for DZ2002 and DZA. This validated assay was applied to a rat pharmacokinetic study of DZ2002. After oral administration, DZ2002 was found to be extensively converted into DZA. The level of systemic exposure to DZ2002 was significantly lower than that of DZA. The apparent oral bioavailability of DZ2002 was 90%-159%. The mean terminal half-lives of DZ2002 and DZA were 0.3-0.9 and 1.3-5.1 h, respectively. The sample preparation method illustrated here may be adopted for determination of other circulating ester drugs and their acid metabolites in rodents. (C) 2019 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. |
| 资助项目 | National Science & Technology Major Project of China 'Key New Drug Creation and Manufacturing Program'[2017ZX09301012-006] ; National Natural Science Foundation of China[81603380] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050306] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000456828800004 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/290714]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Chuan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Chinese Acad Sci, Beijing 100049, Peoples R China 3.Fudan Univ, Shanghai Canc Ctr, Shanghai 200032, Peoples R China 4.Tianjin Univ Tradit Chinese Med, Tianjin, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jia, Weiwei,Li, Jing,Du, Feifei,et al. Assay development for determination of DZ2002, a new reversible SAHH inhibitor, and its acid metabolite DZA in blood and application to rat pharmacokinetic study[J]. JOURNAL OF PHARMACEUTICAL ANALYSIS,2019,9(1):25-33. |
| APA | Jia, Weiwei.,Li, Jing.,Du, Feifei.,Sun, Yan.,Xu, Fang.,...&Li, Chuan.(2019).Assay development for determination of DZ2002, a new reversible SAHH inhibitor, and its acid metabolite DZA in blood and application to rat pharmacokinetic study.JOURNAL OF PHARMACEUTICAL ANALYSIS,9(1),25-33. |
| MLA | Jia, Weiwei,et al."Assay development for determination of DZ2002, a new reversible SAHH inhibitor, and its acid metabolite DZA in blood and application to rat pharmacokinetic study".JOURNAL OF PHARMACEUTICAL ANALYSIS 9.1(2019):25-33. |
入库方式： OAI收割
来源：上海药物研究所
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