北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学药学院  > 化学生物学系  > 期刊论文
学科主题: 药学
题名:
LC and LC-MS Study of the Bioavailability and Metabolites of TM208 after Oral and Intravenous Administration to Rat
作者: Wang, Jiao1; Song, Yan2; Zhang, Jianmei1; Li, Xiaona1; Ling, Xiaomei1,2; Li, Runtao2; Cui, Jingrong2
关键词: Column liquid chromatography ; Mass spectrometry ; Bioavailability ; Metabolites ; Dithiocarbamate
刊名: CHROMATOGRAPHIA
发表日期: 2010-09-01
DOI: 10.1365/s10337-010-1697-4
卷: 72, 期:5-6, 页:459-464
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemical Research Methods ; Chemistry, Analytical
研究领域[WOS]: Biochemistry & Molecular Biology ; Chemistry
关键词[WOS]: 3-CYANO-3,3-DIPHENYLPROPYL ESTER HYDROCHLORIDE ; TANDEM MASS-SPECTROMETRY ; HPLC
英文摘要:

4-Methylpiperazine-1-carbodithioic acid 3-cyano-3,3-diphenylpropyl ester hydrochloride (TM208) is a new compound expected to become a new drug because of excellent in vivo and in vitro anticancer activity and low toxicity. A new, specific and sensitive LC method was set up for detecting the bioavailability of TM208 after oral administration. Samples were extracted with ethyl acetate after oral and intravenous administration. The retention times of TM208 and plunarizine (I.S.) were 5.5 and 9.9 min, respectively. The linear range was 0.125-50 mu g mL(-1). The accuracy (error, %) for three concentrations was 2.7-16.6%. Intra-day precision (as RSD) was 1.6-6.9% and inter-day precision was 7.6-11.5%. Extraction recovery of TM208 was 84.15-89.51% and that of the I.S. was 83.3%. Results from stability testing indicated that samples should be analyzed within 24 h or frozen immediately for later analysis. The bioavailable fraction (F) calculated by use of a non-compartment model was 63.3%. Pharmacokinetic data for TM208 were: mean residence time 24.3 and 5.1 h, V (d) 186.2 and 35.5 L kg(-1), and Cl 6.9 and 4.2 L h(-1) kg(-1) after oral and intravenous administration, respectively. LC-MS comparison of the metabolites after the two methods of administration showed the kind and content of metabolites of TM208 in rat urine after intravenous administration were more than after oral administration. The experimental results show that the low anticancer activity of TM208 after intravenous administration is related to rapid elimination of the drug, and that the kind and content of metabolites do not affect the bioactivity of TM208.

语种: 英语
所属项目编号: 7102107 ; K20090207 ; 2009ZX 09301-010
项目资助者: Natural Science Foundation of Beijing ; Open Foundation of the State Key Laboratory of Natural and Biomimetic Drugs ; National New Drug Research and Development Project of China
WOS记录号: WOS:000281174300013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63822
Appears in Collections:北京大学药学院_化学生物学系_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut Anal, Beijing 100191, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Jiao,Song, Yan,Zhang, Jianmei,et al. LC and LC-MS Study of the Bioavailability and Metabolites of TM208 after Oral and Intravenous Administration to Rat[J]. CHROMATOGRAPHIA,2010,72(5-6):459-464.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Wang, Jiao]'s Articles
[Song, Yan]'s Articles
[Zhang, Jianmei]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Wang, Jiao]‘s Articles
[Song, Yan]‘s Articles
[Zhang, Jianmei]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace