title: Determination of PF-04620110, a novel inhibitor of diacylglycerol acyltransferase-1, in rat plasma using liquid chromatography-tandem mass spectrometry and its application in pharmacokinetic studies.
abstract: In this study, we developed a method for the determination of PF-04620110 (2-{(1r,4r)-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT-1) inhibitor, in rat plasma and validated it using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC-MS/MS system for quantification. PF-04620110 and imipramine (internal standard) were separated using a Hypersil Gold C18 column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive-ion mode [M + H](+) of multiple-reaction monitoring were m/z 397.0 → 260.2 for PF-04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF-04620110 at concentrations within the range 0.05-50 µg/mL and the signal-to-noise ratios for the samples were ≥10. The intra- and inter-day precision and accuracy of the method matched the acceptance criteria for assay validation. PF-04620110 was stable under various processing and/or handling conditions. PF-04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF-04620110, suggesting that the assay is useful for pharmacokinetic studies in rats.
authors: Drug Discovery Platform Technology Team, Korea Research Institute of Chemical Technology, Daejon, 305-343, Republic of Korea.
authors: Kyeong-Ryoon
authors: KR
authors: Lee
authors: Sung Heum
authors: SH
authors: Choi
authors: Jin-Sook
authors: JS
authors: Song
authors: Hyewon
authors: H
authors: Seo
authors: Yoon-Jee
authors: YJ
authors: Chae
authors: Hwang Eui
authors: HE
authors: Cho
authors: Jin Hee
authors: JH
authors: Ahn
authors: Sung-Hoon
authors: SH
authors: Ahn
authors: Myung Ae
authors: MA
authors: Bae
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D010077:Oxazepines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010077:Oxazepines; C582730:PF-04620110; D051048:Diacylglycerol O-Acyltransferase