assaydevelopmentfordeterminationofdz2002anewreversiblesahhinhibitoranditsacidmetabolitedzainbloodandapplicationtoratpharmacokineticstudy

	assaydevelopmentfordeterminationofdz2002anewreversiblesahhinhibitoranditsacidmetabolitedzainbloodandapplicationtoratpharmacokineticstudy
	Weiwei Jia 1; Jing Li 1; Feifei Du 1; Yan Sun 3; Fang Xu 1; Fengqing Wang 1; Olajide E Olaleye 1; Danghui Chen 1; Wei Tang 1; Jianping Zuo 1
刊名	药物分析学报英文版
	2019
卷号	009 期号:001 页码:25
关键词	S-adenosyl-L-homocysteine hydrolase DZ2002 Carboxylesterases Pharmacokinetics
ISSN号	2095-1779
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.
资助项目	[National Science & Technology Major Project of China 'Key New Drug Creation and Manufacturing Program'] ; [National Natural Science Foundation of China] ; [Strategic Priority Research Program of the Chinese Academy of Sciences]
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/283047]
专题	中国科学院上海药物研究所
作者单位	1.中国科学院上海药物研究所 2.中国科学院大学 3.复旦大学
推荐引用方式 GB/T 7714	Weiwei Jia,Jing Li,Feifei Du,et al. assaydevelopmentfordeterminationofdz2002anewreversiblesahhinhibitoranditsacidmetabolitedzainbloodandapplicationtoratpharmacokineticstudy[J]. 药物分析学报英文版,2019,009(001):25.
APA	Weiwei Jia.,Jing Li.,Feifei Du.,Yan Sun.,Fang Xu.,...&Chuan Li.(2019).assaydevelopmentfordeterminationofdz2002anewreversiblesahhinhibitoranditsacidmetabolitedzainbloodandapplicationtoratpharmacokineticstudy.药物分析学报英文版,009(001),25.
MLA	Weiwei Jia,et al."assaydevelopmentfordeterminationofdz2002anewreversiblesahhinhibitoranditsacidmetabolitedzainbloodandapplicationtoratpharmacokineticstudy".药物分析学报英文版 009.001(2019):25.