Bioanalysis of zosuquidar trihydrochloride (LY335979) in small volumes of human and murine plasma by ion-pairing reversed-phase high-performance liquid chromatography.
J Chromatogr B Analyt Technol Biomed Life Sci
; 798(1): 63-8, 2003 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-14630360
ABSTRACT
We have developed and validated a sensitive and selective method for the quantitative determination of the P-glycoprotein inhibitor zosuquidar (LY335979) in human and murine plasma using only 50 microl sample volumes. Sample pretreatment involved liquid-liquid extraction with tert-butyl methyl ether. Zosuquidar and the internal standard chlorpromazine were separated using a narrow bore column (2.1 mm x 150 mm) packed with 3.5 microm symmetry C(18) material. The mobile phase consisted of 38% (v/v) acetonitrile in 50mM ammonium acetate buffer pH 3.8 containing 0.005 M 1-octyl sulfonic acid and was delivered at 0.2 ml/min. Detection was performed with a fluorescence detector set at an excitation wavelength of 260 nm and an emission wavelength of 460 nm. The calibration curve was prepared in blank human plasma and was linear over the dynamic range (10-1000 ng/ml). The lower limit of quantitation was 20 ng/ml. The validation results showed that the assay was selective and reproducible. Within the range of the calibration curve the accuracy was close to 100% and within-day and between-day precision were within the generally accepted 15% range. This method was applied to study the pharmacokinetics of i.v. administered zosuquidar in mice. The sensitivity of the assay was sufficient to determine the drug concentration in plasma samples obtained up to 24 h after administration.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Cromatografia Líquida de Alta Pressão
/
Dibenzocicloeptenos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Chromatogr B Analyt Technol Biomed Life Sci
Assunto da revista:
ENGENHARIA BIOMEDICA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Holanda