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用于测定新型组蛋白去乙酰化酶抑制剂肯丁91在小鼠血浆和组织中的液相色谱-串联质谱法的开发与验证:在药代动力学研究中的应用

Development and validation of a liquid chromatography-tandem mass spectrometry for the determination of Kendine 91, a novel histone deacetylase inhibitor, in mice plasma and tissues: application to a pharmacokinetic study.

作者信息

Otaegui Dorleta, Rodríguez-Gascón Alicia, Zubia Aizpea, Cossío Fernando P, Pedraz José Luis

机构信息

Organic Chemistry Department, Faculty of Chemistry, University of the Basque Country, Edificio Joxe Mari Korta, Av Tolosa 72, San Sebastián, Spain.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 1;870(1):109-16. doi: 10.1016/j.jchromb.2008.06.013. Epub 2008 Jun 13.

Abstract

A liquid chromatography-tandem mass spectrometric method (LC-MS/MS) has been developed and validated to determine the concentration of Kendine 91 in mice plasma and tissues. Simvastatin was employed as the internal standard. Separation was performed on a C8 column, with a mobile phase consisting of methanol and aqueous 10 mM formic acid (73:27 v/v). Both analyte and internal standard were determined using electrospray ionization and the MS data acquisition was via multiple-reaction monitoring (MRM) in positive scanning mode. Quantification was performed using the transitions m/z 444-->169 and 441-->325 for Kendine 91 and simvastatin, respectively. The method was validated with respect to linearity, accuracy, precision, recovery and stability. This assay has been successfully applied to a pharmacokinetic study after intravenous injection of Kendine 91 in mice in a dose of 10mg/kg.

摘要

已开发并验证了一种液相色谱 - 串联质谱法(LC-MS/MS),用于测定小鼠血浆和组织中Kendine 91的浓度。辛伐他汀用作内标。在C8柱上进行分离,流动相由甲醇和10 mM甲酸水溶液(73:27 v/v)组成。使用电喷雾电离测定分析物和内标,通过正扫描模式下的多反应监测(MRM)进行MS数据采集。分别使用m/z 444-->169和441-->325的跃迁对Kendine 91和辛伐他汀进行定量。该方法在线性、准确性、精密度、回收率和稳定性方面得到了验证。该测定法已成功应用于以10mg/kg剂量静脉注射Kendine 91后小鼠的药代动力学研究。

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