Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1167316 | Analytica Chimica Acta | 2011 | 8 Pages |
Abstract
(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 °C for 1 h. The analytes are separated on a Gemini 5 μm 100 Ã
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 mLâ1. The validation results show accuracy (%RE < 11.7) and precision (%RSD < 8.6) at a broad linear dynamic range (0.030-100 ng mLâ1). 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.
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Jia Liu, Xiaoyan Chen, Yifan Zhang, Hong Miao, Ke Liu, Liang Li, Dafang Zhong,