Quantitative determination of clopidogrel active metabolite in human plasma by LC-MS/MS.
J Pharm Biomed Anal
; 48(4): 1219-24, 2008 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-18829199
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ticlopidina
/
Inibidores da Agregação Plaquetária
/
Cromatografia Líquida
/
Espectrometria de Massas em Tandem
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Pharm Biomed Anal
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Japão