Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan, 570-749, Korea.
Arch Pharm Res. 2009 Dec;32(12):1743-8. doi: 10.1007/s12272-009-2212-z. Epub 2010 Feb 17.
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.
PAR-5359，3-(4-{2-[4-(4-氯苯基)-3,6-二氢-2H-吡啶-1-基]-乙氧基}-苯基)-2-乙氧基丙酸，是一种具有良好平衡的 PPARalpha/gamma 双重激动剂，具有优异的降血糖和降血脂活性。建立了一种可靠、选择性和灵敏的高效液相色谱-电喷雾串联质谱法，用于测定大鼠血浆中的 PAR-5359。PAR-5359 在中性 pH 下用甲基叔丁基醚从大鼠血浆中两次提取。分析物在 Allure Biphenyl 柱上用 78%甲醇在 10 mM 甲酸铵（pH 3.0）的流动相分离，并通过串联质谱在选择性反应监测模式下检测。校准曲线在 2.00-1000.0 ng/mL 浓度范围内呈线性（r = 0.9993），使用 50 μL 血浆样品时定量下限为 2.00 ng/mL。四个 QC 水平的变异系数和相对误差分别为 1.2-12.3%和-2.5-6.3%。该方法成功应用于雄性 SD 大鼠口服 1 mg/kg PAR-5359 后 PAR-5359 的药代动力学研究。
