Quantitative determination of odanacatib in human plasma using liquid-liquid extraction followed by liquid chromatography-tandem mass spectrometry analysis.
J Chromatogr B Analyt Technol Biomed Life Sci
; 885-886: 15-23, 2012 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-22230741
ABSTRACT
Odanacatib (ODN, MK-0822) is an investigational drug under development for the treatment of osteoporosis. A quantitative LC/MS-MS methodology was developed and validated to determine ODN concentrations in human plasma, with a linear calibration range from 0.500 to 500ng/mL. Stable isotope (13)C(6)-labeled ODN was employed as the internal standard (IS). Sample preparation was based on liquid-liquid extraction of basified plasma with methyl t-butyl ether in a 96-well plate format. The extracted samples were analyzed on a liquid chromatography-tandem mass spectrometry system equipped with a turbo ion spray source. Chromatographic separation of the analyte and IS was achieved on a Phenomenex Luna C18 (50mm×2.0mm, 5µm) column. Ion pairs m/z 526â313 for the analyte and m/z 532â319 for the IS were monitored in positive ionization mode for MS detection. This methodology has been fully validated and proved to be rugged and reproducible. Intra- and inter-run variability was within 5.88%, with accuracy between 95.6 and 106% of the nominal concentrations. Analyte stability was evaluated under various sample preparation, analysis and storage conditions. This assay has been utilized to analyze human plasma samples obtained from phase I to III clinical trials.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Bifenilo
/
Cromatografia Líquida
/
Espectrometria de Massas em Tandem
/
Extração Líquido-Líquido
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Chromatogr B Analyt Technol Biomed Life Sci
Assunto da revista:
ENGENHARIA BIOMEDICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos