Bioanalysis of zosuquidar trihydrochloride (LY335979) in small volumes of human and murine plasma by ion−pairing reversed-phase high-performance liquid chromatography
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 μl sample volumes. Sample pretreatment involved liquid-liquid extraction with tert-butyl methyl ether. Zo...
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Published in | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 798; no. 1; pp. 63 - 68 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier B.V
05.12.2003
Elsevier Science |
Subjects | |
Online Access | Get full text |
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Summary: | 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
μl 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×150
mm) packed with 3.5
μm symmetry C
18 material. The mobile phase consisted of 38% (v/v) acetonitrile in 50
mM 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1570-0232 1873-376X |
DOI: | 10.1016/j.jchromb.2003.08.047 |