Abstract |
An assay method for the determination of oltipraz, a candidate drug for the treatment of liver fibrosis and liver cirrhosis, was developed in rat plasma using a fast-flow protein precipitation (FF-PPT) method coupled with LC-MS/MS for quantification to reduce the labor and to improve the speed of analysis. The applicability of the assay to pharmacokinetic studies was also evaluated. Oltipraz and ethyl- oltipraz, an internal standard (IS), were analyzed by multiple reaction monitoring (MRM) at m/z transitions of 227→193 and 241→174, respectively. A lower limit of quantification (LLOQ) of 20 ng/mL was observed, with a linear dynamic range from 20 to 4000 ng/mL (R>0.997). The accuracy, precision, dilution, recovery, and stability of the assay were deemed acceptable according to FDA guidelines. Oltipraz concentrations were measured successfully in plasma samples up to 12h post-dose in rats that had received an oral dose of 60 mg/kg. The findings indicate that the assay method is rapid and sensitive to oltipraz, showing applicability for pharmacokinetics (PK) studies of oltipraz in other small animals, including rats.
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Authors | Jong-Hwa Lee, Hwanmi Lim, Do-Geun Kim, Dae-Hun Park, Young-Ah Woo, Hyun-Jung Noh, Qing-Ri Jin, Kyeong-Ryoon Lee, Gye-Won Lee, Choong-Yong Kim |
Journal | Journal of pharmaceutical and biomedical analysis
(J Pharm Biomed Anal)
Vol. 56
Issue 3
Pg. 623-6
(Nov 01 2011)
ISSN: 1873-264X [Electronic] England |
PMID | 21757314
(Publication Type: Journal Article)
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Copyright | Copyright © 2011 Elsevier B.V. All rights reserved. |
Chemical References |
- Pyrazines
- Thiones
- Thiophenes
- oltipraz
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Topics |
- Animals
- Calibration
- Chromatography, High Pressure Liquid
(methods)
- Drug Monitoring
(methods)
- Drug Stability
- Pyrazines
(blood, pharmacokinetics)
- Rats
- Reference Standards
- Reproducibility of Results
- Sensitivity and Specificity
- Tandem Mass Spectrometry
(methods)
- Thiones
- Thiophenes
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