Linked Life Data

20143781

Source:http://linkedlifedata.com/resource/pubmed/id/20143781

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-3-1
pubmed:abstractText
Nucleoside reverse transcriptase inhibitors (NRTI) require intracellular phosphorylation, which involves multiple enzymatic steps to inhibit the human immunodeficiency virus type 1 (HIV-1). NRTI-triphosphates (NRTI-TP) compete with endogenous 2'-deoxyribonucleosides-5'-triphosphates (dNTP) for incorporation by the HIV-1 reverse transcriptase (RT). Thus, a highly sensitive analytical methodology capable of quantifying at the low femtomoles/10(6) cells level was necessary to understand the intracellular metabolism and antiviral activity of NRTIs in human peripheral blood mononuclear (PBM) cells and in macrophages. A novel, rapid, and a reproducible ion-pair chromatography-tandem mass spectrometry (MS/MS) method was developed to simultaneously quantify the intracellular phosphorylated metabolites of abacavir, emtricitabine, tenofovir disoproxil fumarate, amdoxovir, and zidovudine, as well as four natural endogenous dNTP. Positive or negative electrospray ionization was chosen with specific MS/MS transitions for improved selectivity on all the compounds studied. The sample preparation, the ion-pair reagent concentration, and buffer composition were optimized, resulting in the simultaneous quantification of 13 different nucleotides in a total run time of 30 min. This novel method demonstrated optimal sensitivity (limit of detection 1-10 nM for various analytes), specificity, and reproducibility to successfully measure NRTI-TP and dNTP in human PBM cells and macrophages.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1520-6882
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1982-9
pubmed:dateRevised
2011-9-30
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Simultaneous quantification of intracellular natural and antiretroviral nucleosides and nucleotides by liquid chromatography-tandem mass spectrometry.
pubmed:affiliation
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30332, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural