Linked Life Data

20872637

Source:http://linkedlifedata.com/resource/pubmed/id/20872637

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2010-9-27
pubmed:abstractText
The use of high-performance liquid chromatography/mass spectrometry (HPLC/MS) and proton nuclear magnetic resonance ((1)H NMR) spectroscopy for the kinetic analysis of acyl glucuronide (AG) isomerisation and hydrolysis of the 1-?-O-acyl glucuronides (1-?-O-AG) of phenylacetic acid, (R)- and (S)-?-methylphenylacetic acid and ?,?-dimethylphenylacetic acid is described and compared. Each AG was incubated in both aqueous buffer, at pH 7.4, and control human plasma at 37°C. Aliquots of these incubations, taken throughout the reaction time-course, were analysed by HPLC/MS and (1)H NMR spectroscopy. In buffer, transacylation reactions predominated, with relatively little hydrolysis to the free aglycone observed. In human plasma incubations the calculated rates of reaction were much faster than for buffer and, in contrast to the observations in buffer, hydrolysis to the free aglycone was a significant contributor to the overall reaction.A diagnostic analytical methodology based on differential mass spectrometric fragmentation of 1-?-O-AGs compared to the 2-, 3- and 4-positional isomers, which enables selective determination of the former, was confirmed and applied. These findings show that HPLC/MS offers a viable alternative to the more commonly used NMR spectroscopic approach for the determination of the transacylation and hydrolysis reactions of these AGs, with the major advantage of having the capability to do so in a complex biological matrix such as plasma.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1097-0231
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 John Wiley & Sons, Ltd.
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3043-51
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
High-performance liquid chromatography/mass spectrometric and proton nuclear magnetic resonance spectroscopic studies of the transacylation and hydrolysis of the acyl glucuronides of a series of phenylacetic acids in buffer and human plasma.
pubmed:affiliation
Department of Clinical Pharmacology, Drug Metabolism and Pharmacokinetics, AstraZeneca Pharmaceuticals, Macclesfield, Cheshire SK10 4TG, UK.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't