title: 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.
authors.affiliation: Toxicology Center, Korea Institute of Toxicology, Jang-dong, Daejeon, Republic of Korea.
authors.forename: Jong-Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Hwanmi
authors.initials: H
authors.lastname: Lim
authors.forename: Do-Geun
authors.initials: DG
authors.lastname: Kim
authors.forename: Dae-Hun
authors.initials: DH
authors.lastname: Park
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Woo
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Noh
authors.forename: Qing-Ri
authors.initials: QR
authors.lastname: Jin
authors.forename: Kyeong-Ryoon
authors.initials: KR
authors.lastname: Lee
authors.forename: Gye-Won
authors.initials: GW
authors.lastname: Lee
authors.forename: Choong-Yong
authors.initials: CY
authors.lastname: Kim
mesh_terms: D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D004355:Drug Stability; D011719:Pyrazines / Q000097:blood* / Q000493:pharmacokinetics*; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013871:Thiones; D013876:Thiophenes
chemical_list: D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz