Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-2-22
pubmed:abstractText
(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 ?m 100 Å 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1873-4324
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
689
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
69-76
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Derivatization of (5R)-hydroxytriptolide from benzylamine to enhance mass spectrometric detection: application to a Phase I pharmacokinetic study in humans.
pubmed:affiliation
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't