Determination of a novel TAZ modulator, 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2鈥?(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H imidazo[4,5-b]pyridine] (TM-25659) in rat plasma by liquid chromatography-tandem mass spectrometry

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• 作者：Sung Heum Choi^a ; Kyeong-Ryoon Lee^a ; Jae-Chun Woo^a ; Nak Jeong Kim^b ; Dong Cheul Moon^c ; Eun Sook Hwang^d ; Sung-Hoon Ahn^a ; Myung Ae Bae^a ; Min-Sun Kim^a ; ^{mskime777@gmail.com} ; ^{smkim9677@naver.com}
• 关键词：TM-25659 ; Method validation ; Pharmacokinetics ; LC&ndash ; MS/MS ; Rat plasma
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2012
• 期刊代码：65_07317085
• 类别：ch
• 出版时间：7 April, 2012
• 卷：63
• 期：Complete
• 页码：47-52
• 文件大小：404 K

摘要

TM-25659 compound, a novel TAZ modulator, is developed for the control of bone loss and obesity. TAZ is known to bind to a variety of transcription factors to control cell differentiation and organ development. A selective and sensitive method was developed for the determination of TM-25659 concentrations in rat plasma. The drug was measured by liquid chromatography-tandem mass spectrometry after liquid-liquid extraction with ethyl acetate. TM-25659 and the internal standard imipramine were separated on a Hypersil GOLD C18 column with a mixture of acetonitrile-ammonium formate (10 mM) (90:10, v/v) as the mobile phase. The ions m/z 501.2 鈫?#xA0;207.2 for TM-25659 and m/z 281.0 鈫?#xA0;86.0 for imipramine in multiple reaction monitoring mode were used for the quantitation. The calibration range was 0.1-100 渭g/ml with a correlation coefficient greater than 0.99. The lower limit of quantitation of TM-25659 in rat plasma was 0.1 渭g/ml. The percent recoveries of TM-25659 and imipramine were 98.6%and 95.7%from rat plasma, respectively. The intra- and inter-batch precisions were 3.17-15.95%and the relative error was 0.38-10.82%. The developed assay was successfully applied to a pharmacokinetic study of TM-25659 administered intravenously (10 mg/kg) to rats.