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Quantification of oltipraz using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study in rat plasma.

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.
AuthorsJong-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
JournalJournal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 56 Issue 3 Pg. 623-6 (Nov 01 2011) ISSN: 1873-264X [Electronic] England
PMID21757314 (Publication Type: Journal Article)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Pyrazines
  • Thiones
  • Thiophenes
  • oltipraz
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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