Source:http://linkedlifedata.com/resource/pubmed/id/15529418
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rdf:type | |
lifeskim:mentions |
umls-concept:C0008565,
umls-concept:C0010762,
umls-concept:C0013227,
umls-concept:C0086418,
umls-concept:C0182400,
umls-concept:C0185125,
umls-concept:C0439831,
umls-concept:C0599748,
umls-concept:C0680730,
umls-concept:C0809874,
umls-concept:C0870883,
umls-concept:C1148554,
umls-concept:C1285572,
umls-concept:C1314763,
umls-concept:C2603343
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pubmed:issue |
23
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pubmed:dateCreated |
2004-11-23
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pubmed:abstractText |
A liquid chromatography/mass spectrometry method, for rapid determination of five cytochrome P450 (CYP) probe drugs and their relevant metabolites in human plasma and urine, is described. The five specific probe substrates/metabolites, caffeine/paraxanthine (CYP1A2), tolbutamide/4-hydroxytolbutamide/carboxytolbutamide (CYP2C9), omeprazole/5-hydroxyomeprazole (CYP2C19), debrisoquine/5-hydroxydebrisoquine (CYP2D6) and midazolam/1'-hydroxymidazolam (CYP3A), together with the internal standards (phenacetin and paracetamol), in plasma and urine, were extracted using solid-phase extraction. The chromatography was performed using a C18 column with an isocratic mobile phase consisting of acetonitrile and 0.1% formic acid in water (70:30). The triple-quadrupole mass spectrometer was operated in both positive and negative modes, and multiple reaction monitoring was used for quantification. The method was validated over the concentration ranges 0.05-5 microg/mL for caffeine and paraxanthine, 0.02-2 microg/mL for tolbutamide, 0.1-20 microg/mL for 4-hydroxytolbutamide, carboxytolbutamide, debrisoquine and 5-hydroxydebrisoquine, 5-2500 ng/mL for omeprazole and 5-hydroxyomeprazole, and 1-100 ng/mL for midazolam and 1'-hydroxymidazolam. The intra- and inter-day precision were 0.3-13.7% and 1.9-14.3%, respectively, and the accuracy ranged from 93.5-107.2%. The lower limit of quantification varied between 1 and 100 ng/mL. The present method provides a robust, fast and sensitive analytical tool for the five-probe drug cocktail, and has been successfully applied to a clinical phenotyping study in 16 subjects.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0951-4198
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pubmed:author | |
pubmed:copyrightInfo |
2004 John Wiley & Sons, Ltd.
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pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2921-33
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15529418-Chromatography, High Pressure Liquid,
pubmed-meshheading:15529418-Cytochrome P-450 Enzyme System,
pubmed-meshheading:15529418-Drug Combinations,
pubmed-meshheading:15529418-Humans,
pubmed-meshheading:15529418-Pharmaceutical Preparations,
pubmed-meshheading:15529418-Phenotype,
pubmed-meshheading:15529418-Reproducibility of Results,
pubmed-meshheading:15529418-Sensitivity and Specificity,
pubmed-meshheading:15529418-Spectrometry, Mass, Electrospray Ionization
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pubmed:year |
2004
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pubmed:articleTitle |
Rapid determination of five probe drugs and their metabolites in human plasma and urine by liquid chromatography/tandem mass spectrometry: application to cytochrome P450 phenotyping studies.
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pubmed:affiliation |
School of Pharmacy, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. qpyin@cuhk.edu.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Validation Studies
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