Determination of a novel TAZ modulator, 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2′-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H imidazo[4,5-b]pyridine] (TM-25659) in rat plasma by liquid chromatography-tandem mass spectrometry
Determination of a novel TAZ modulator, 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2′-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H imidazo[4,5-b]pyridine] (TM-25659) in rat plasma by liquid chromatography-tandem mass spectrometry
复制标题
DOI：
10.1016/j.jpba.2012.01.036
复制
发表时间：
2012-04-07
影响因子：
3.4
通讯作者：
Kim, Min-Sun
中科院分区：
文献类型：
--
作者：
Choi, Sung Heum;Lee, Kyeong-Ryoon;Kim, Min-Sun
TM - 25659化合物是一种新型的TAZ调节剂，被开发用于控制骨质流失和肥胖。已知TAZ会与多种转录因子结合以控制细胞分化和器官发育。建立了一种选择性和灵敏的方法用于测定大鼠血浆中TM - 25659的浓度。采用乙酸乙酯液 - 液萃取后，通过液相色谱 - 串联质谱法对药物进行测定。TM - 25659和内标丙咪嗪在Hypersil GOLD C18柱上进行分离，以乙腈 - 甲酸铵（10 mM）（90:10，v/v）的混合物作为流动相。在多反应监测模式下，TM - 25659的离子m/z 501.2 -> 207.2以及丙咪嗪的离子m/z 281.0 -> 86.0用于定量。校准范围为0.1 - 100μg/ml，相关系数大于0.99。大鼠血浆中TM - 25659的定量下限为0.1μg/ml。TM - 25659和丙咪嗪从大鼠血浆中的回收率分别为98.6%和95.7%。批内和批间精密度为3.17 - 15.95%，相对误差为0.38 - 10.82%。所建立的分析方法成功应用于大鼠静脉注射（10 mg/kg）TM - 25659的药代动力学研究。（C）2012爱思唯尔有限公司。保留所有权利。
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 -> 207.2 for TM-25659 and m/z 281.0 -> 86.0 for imipramine in multiple reaction monitoring mode were used for the quantitation. The calibration range was 0.1-100 mu g/ml with a correlation coefficient greater than 0.99. The lower limit of quantitation of TM-25659 in rat plasma was 0.1 mu 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. (C) 2012 Elsevier B.V. All rights reserved.