Linked Life Data

10975250

Source:http://linkedlifedata.com/resource/pubmed/id/10975250

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-1-18
pubmed:abstractText
CGS 26214 is a racemic compound having cholesterol-lowering activity in rats, dogs, and monkeys. This compound has two equipotent chiral components CGS 28934(-) and CGS 28935(+). An analytical challenge was to develop a sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the analysis of the chiral components in human plasma following clinical doses of 1 mg or less. Several issues had to be addressed in order to devise a LC/MS/MS assay for the above compounds. First, the compounds were esters and susceptible to hydrolysis under experimental conditions. Second, a lower limit of quantitation (LLOQ) of 0.4 ng/ml was needed. Third, positive electrospray ionization of CGS 26214 did not yield sufficient sensitivity needed for the studies in humans. Consequently, LC/MS/MS conditions were optimized for negative ion mode of detection. Fourth, sample preparation steps proved to be critical in order to reduce the possibility of microbore chiral-HPLC column (100 x 1.0 mm i.d.) obstruction, chromatographic deterioration, and matrix mediated electrospray ion suppression. Although the present method addressed the above challenges, its major drawback was limited sample throughput capability. Nonetheless, the method was successfully applied to generate plasma concentration-time profiles for human subjects after oral doses (0.9 mg) of the racemate as well as the optically pure isomers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0731-7085
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
745-55
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Determination of the chiral isomers of CGS 26214, a synthetic thyromimetic agent, in human plasma using microbore chiral chromatography-tandem mass spectrometry.
pubmed:affiliation
Department of Drug Metabolism and Pharmacokinetics, Novartis Institute for Biomedical Research, East Hanover, NJ 07936, USA. tapan.majumdar@pharma.novartis.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't