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KMID : 0043320090320121743
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Archives of Pharmacal Research
2009 Volume.32 No. 12 p.1743 ~ p.1748
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Liquid Chromatography-Tandem Mass Spectrometry of a New PPARα/γ Dual Agonist PAR-5359 in Rat Plasma
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Lee Hye-Suk
Kim Dong-Kyun
Park Eun-Jeong
Jeong Ji-Hyun
Jeon Sun-Ho
Kim Eun-Jung
Shim Hyun-Joo
Lim Joong-In
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Abstract
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PAR-5359, 3-(4-{2-[4-(4-Chloro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-ethoxy}-phenyl)-2-ethoxypropionic acid, is a well-balanced PPARα/γ dual agonist with the excellent antihyperglycemic and hypolipidemic activities. A reliable, selective and sensitive high-performance liquid chromatography with electrospray ionization tandem mass spectrometry was developed for the determination of PAR-5359 in rat plasma. PAR-5359 was twice extracted from rat plasma using methyl tert-butyl ether at neutral pH. The analytes were separated on an Allure Biphenyl column with the mobile phase of 78% methanol in 10 mM ammonium formate (pH 3.0) and detected by tandem mass spectrometry in the selective reaction monitoring mode. The calibration curve was linear (r = 0.9993) over the concentration range of 2.00-1000.0 ng/mL and the lower limit of quantification was 2.00 ng/mL using 50 μL plasma sample. The coefficient of variation and relative error at four QC levels were 1.2 to 12.3% and -2.5 to 6.3%, respectively. The present method was successfully applied to the pharmacokinetic study of PAR-5359 after oral dose of PAR-5359 at a dose of 1 mg/kg to male SD rats.
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KEYWORD
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PAR-5359, LC/MS/MS, Rat plasma
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