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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-12-29
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0731-7085
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1219-24
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
pubmed:year
2008
pubmed:articleTitle
Quantitative determination of clopidogrel active metabolite in human plasma by LC-MS/MS.
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
pubmed:publicationType
Journal Article