title: Liquid chromatography-tandem mass spectrometry of a new PPARalpha/gamma dual agonist PAR-5359 in rat plasma.
abstract: 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 PPARalpha/gamma 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 microL 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.
authors.affiliation: Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan, 570-749, Korea.
authors.forename: Dong Kyun
authors.initials: DK
authors.lastname: Kim
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Park
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Jeong
authors.forename: Sun Ho
authors.initials: SH
authors.lastname: Jeon
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Kim
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Shim
authors.forename: Joong In
authors.initials: JI
authors.lastname: Lim
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D007004:Hypoglycemic Agents / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D011422:Propionates / Q000097:blood* / Q000493:pharmacokinetics*; D011725:Pyridines / Q000097:blood* / Q000493:pharmacokinetics*; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D000077154:Rosiglitazone; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D045162:Thiazolidinediones / Q000097:blood / Q000493:pharmacokinetics
chemical_list: C532944:(3-(4-(2(4-(4chloro-phenyl)-3,6-dihydro-2H-pyridin-1-yl)-ethoxy)-phenyl)-(2S)-ethoxy-propionic acid); D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D011422:Propionates; D011725:Pyridines; D045162:Thiazolidinediones; D000077154:Rosiglitazone