Quantification of oltipraz using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study in rat plasma |
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Authors: | Lee Jong-Hwa Lim Hwanmi Kim Do-Geun Park Dae-Hun Woo Young-Ah Noh Hyun-Jung Jin Qing-Ri Lee Kyeong-Ryoon Lee Gye-Won Kim Choong-Yong |
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Institution: | a Toxicology Center, Korea Institute of Toxicology, Jang-dong, Daejeon, Republic of Korea b Pharmaceutical R&D Center, Korea United Pharm. Inc., Jeondong-myeon, Yeongi-kun, Chungnam, Republic of Korea c Pharmaceutical Research Inst., Cheiljedang Corp., Majang-myeon, Icheon, Kyonggi, Republic of Korea d Department of Pharmaceutics, College of Pharmacy, Seoul National University, San 56-1, Shilim-dong, Kwanak-gu, Seoul, Republic of Korea e Pharmaceutical Engineering, Health Sciences, Konyang University, Nonsan, Republic of Korea |
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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 12 h 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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Keywords: | Oltipraz Pharmacokinetics LC-MS/MS FF-PPT Rats |
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