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![]() ![]() ![]() ![]() ![]() |
刊名 | ANALYTICA CHIMICA ACTA
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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 |
DOI | 10.1016/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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