Source:http://linkedlifedata.com/resource/pubmed/id/18829199
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2008-12-29
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pubmed:abstractText |
A quantitative method for the determination of clopidogrel active metabolite (AM) in human plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Clopidogrel AM contains a thiol group, thus requiring stabilization in biological samples. The alkylating reagent 2-bromo-3'-methoxyacetophenone was used to stabilize clopidogrel AM in blood. An analog of the derivatized clopidogrel AM was used as the internal standard (IS). The derivatized samples were subjected to solid-phase extraction with a C2 disk plate and the overall procedure exhibited good reaction (more than 90%) and recovery efficiencies (from 85% to 105%). The derivative of clopidogrel AM (MP-AM) and IS were separated on an ODS column and quantified by tandem mass spectrometry with electrospray ionization. No significant endogenous peaks corresponding to MP-AM or IS were detected in blank human plasma samples, and no significant matrix effect was observed for MP-AM and IS in human plasma samples (from 102% to 121%). The calibration curve ranged from 0.5 to 250 ng/mL with good linearity, and extended by validation of a 50-fold dilution. In the intra- and inter-assay reproducibility tests, the accuracy and precision were within 12% relative error and 6% coefficient of variation, respectively. The derivatized MP-AM was stable in human plasma for 4 months at -80 degrees C. The validated method was successfully used to analyze clinical samples and determine the pharmacokinetics of clopidogrel AM.
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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:month |
Dec
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pubmed:issn |
0731-7085
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1219-24
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pubmed:meshHeading |
pubmed-meshheading:18829199-Adolescent,
pubmed-meshheading:18829199-Adult,
pubmed-meshheading:18829199-Aged,
pubmed-meshheading:18829199-Area Under Curve,
pubmed-meshheading:18829199-Calibration,
pubmed-meshheading:18829199-Chromatography, Liquid,
pubmed-meshheading:18829199-Drug Stability,
pubmed-meshheading:18829199-Female,
pubmed-meshheading:18829199-Freezing,
pubmed-meshheading:18829199-Humans,
pubmed-meshheading:18829199-Male,
pubmed-meshheading:18829199-Metabolic Clearance Rate,
pubmed-meshheading:18829199-Middle Aged,
pubmed-meshheading:18829199-Molecular Structure,
pubmed-meshheading:18829199-Platelet Aggregation Inhibitors,
pubmed-meshheading:18829199-Reference Standards,
pubmed-meshheading:18829199-Reproducibility of Results,
pubmed-meshheading:18829199-Solid Phase Extraction,
pubmed-meshheading:18829199-Spectrometry, Mass, Electrospray Ionization,
pubmed-meshheading:18829199-Tandem Mass Spectrometry,
pubmed-meshheading:18829199-Ticlopidine,
pubmed-meshheading:18829199-Time Factors,
pubmed-meshheading:18829199-Young Adult
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pubmed:year |
2008
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pubmed:articleTitle |
Quantitative determination of clopidogrel active metabolite in human plasma by LC-MS/MS.
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pubmed:affiliation |
Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. takahashi.makoto.zx@daiichisankyo.co.jp
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pubmed:publicationType |
Journal Article
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