中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Derivatization of (5R)-hydroxytriptolide from benzylamine to enhance mass spectrometric detection: Application to a Phase I pharmacokinetic study in humans

文献类型:期刊论文

作者Liu, Jia2; Chen, Xiaoyan2; Zhang, Yifan2; Miao, Hong1; Liu, Ke2; Li, Liang2; Zhong, Dafang2
刊名ANALYTICA CHIMICA ACTA
出版日期2011-03-09
卷号689期号:1页码:69-76
关键词(5R)-Hydroxytriptolide Triptolide Benzylamine Derivatization Liquid chromatography-tandem mass spectrometry Human plasma
ISSN号0003-2670
DOI10.1016/j.aca.2011.01.016
文献子类Article
英文摘要(5R)-Hydroxytriptolide, a semisynthetic structural analog of triptolide, exhibits anti-inflammatory and immunosuppressive effect both in vitro and in vivo. The compound is currently undergoing Phase I clinical trials. This work describes the quantification of (5R)-hydroxytriptolide in human plasma based on chemical derivatization from benzylamine. Analysis through liquid chromatography-tandem mass spectrometry (LC-MS/MS) is performed for characterization. The primary reaction product between (5R)hydroxytriptolide and benzylamine was identified as a 12,13-epoxide ring adduct. For quantification in plasma, (5R)-hydroxytriptolide and the internal standard (triptolide) were first extracted from diethyl ether-dichloromethane (3:2, v/v) and then converted to their benzylamine derivates at 80 degrees C for 1 h. The analytes are separated on a Gemini 5 mu m 100 angstrom column, using a gradient elution program with a solvent consisting of 0.77 mM ammonium hydroxide (pH 10.0) and acetonitrile. An API 4000 tandem mass spectrometer operated in positive ion mode and equipped with an electrospray ionization source is used as detector. This method allows for a lower limit of quantification of 0.030 ng mL(-1). The validation results show accuracy (%RE < 11.7) and precision (%RSD < 8.6) at a broad linear dynamic range (0.030-100 ng mL(-1)). The simple and quantitative derivatization coupled with tandem mass spectrometric analysis yields a sensitive and robust method for the quantification of (5R)-hydroxytriptolide in Phase I pharmacokinetic studies. (C) 2011 Elsevier B.V. All rights reserved.
WOS关键词PERFORMANCE LIQUID-CHROMATOGRAPHY ; PH MOBILE PHASES ; BASIC COMPOUNDS ; TRIPTOLIDE ; (5R)-5-HYDROXYTRIPTOLIDE ; SENSITIVITY ; STRATEGIES ; ARTHRITIS ; PLASMA ; DRUGS
资助项目National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2009ZX09301-001] ; Natural Science Foundation of China[30901831]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000288345900011
出版者ELSEVIER SCIENCE BV
源URL[http://119.78.100.183/handle/2S10ELR8/278583]  
专题上海药物代谢研究中心
通讯作者Zhong, Dafang
作者单位1.Shanghai Pharmaceut Grp Co Ltd, Res Inst, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714
Liu, Jia,Chen, Xiaoyan,Zhang, Yifan,et al. Derivatization of (5R)-hydroxytriptolide from benzylamine to enhance mass spectrometric detection: Application to a Phase I pharmacokinetic study in humans[J]. ANALYTICA CHIMICA ACTA,2011,689(1):69-76.
APA Liu, Jia.,Chen, Xiaoyan.,Zhang, Yifan.,Miao, Hong.,Liu, Ke.,...&Zhong, Dafang.(2011).Derivatization of (5R)-hydroxytriptolide from benzylamine to enhance mass spectrometric detection: Application to a Phase I pharmacokinetic study in humans.ANALYTICA CHIMICA ACTA,689(1),69-76.
MLA Liu, Jia,et al."Derivatization of (5R)-hydroxytriptolide from benzylamine to enhance mass spectrometric detection: Application to a Phase I pharmacokinetic study in humans".ANALYTICA CHIMICA ACTA 689.1(2011):69-76.

入库方式: OAI收割

来源:上海药物研究所

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