Intracerebral microdialysis coupled to LC-MS/MS for the determination tramadol and its major pharmacologically active metabolite O-desmethyltramadol in rat brain microdialysates
Intracerebral microdialysis coupled to LC-MS/MS for the determination tramadol and its major pharmacologically active metabolite O-desmethyltramadol in rat brain microdialysates
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DOI：
10.1002/dta.2157
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发表时间：
2017-08-01
影响因子：
2.9
通讯作者：
Yue, Jiang
中科院分区：
文献类型：
--
作者：
Liu, Mingzhou;Wang, Peng;Yue, Jiang
采用液相色谱-电喷雾串联质谱（LC-ESI-MS/MS）联用脑内微透析技术，建立了曲马多及其主要活性代谢物o -去甲基曲马多（O-desmethyltramadol， ODT）在大鼠脑内的快速、灵敏测定和药动学研究方法。微透析样品在C18柱上分离，流动相为乙腈-水-甲酸（50:50:0.1;v/v/v），流速为0.3 mL/min。电喷雾正离子模式下进行ESI-MS/MS谱分析，曲马多采用m/z [m + H](+) 264.3 -> 58.2， ODT采用m/z [m + H](+) 250.3 -> 58.3，氨溴索（内标；IS）采用m/z [m + H](+) 379.4 -> 264.0的多反应监测。总运行时间为4.0分钟。曲马多的定量下限为1 ng/mL， ODT的定量下限为0.5 ng/mL，曲马多的浓度范围为1近似于500 ng/mL (r > 0.99)， ODT的浓度范围为0.5近似于50 ng/mL (r > 0.99)，线性关系良好。该方法已成功应用于曲马多和ODT在大鼠脑内的药动学研究。版权所有：John Wiley & Sons， Ltd。
A rapid and sensitive method involving liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) coupled to an intracerebral microdialysis technique was developed for the determination and pharmacokinetic investigation of tramadol and its major active metabolite O-desmethyltramadol (ODT) in rat brain. The microdialysis samples were separated on a C18 column and elutedwith a mobile phase of acetonitrile-water-formic acid (50: 50: 0.1; v/v/v) at a flow rate of 0.3 mL/min. The ESI-MS/MS spectra were performed in electrospray positive ion mode, and the analytes were detected by multiple reaction monitoring (MRM) of the transitions m/z [M + H](+) 264.3 -> 58.2 for tramadol, m/z [M + H](+) 250.3 -> 58.3 for ODT, and m/z [M + H](+) 379.4 -> 264.0 for ambroxol (internal standard; IS). The total run time was 4.0 min. A lower limit of quantitation (LLOQ) was achieved as 1 ng/mL for tramadol and 0.5 ng/mL for ODT, with excellent linearity over a concentration range of 1 similar to 500 ng/mL (r > 0.99) for tramadol and 0.5 similar to 50 ng/mL for ODT (r > 0.99), respectively. The proposed method was successfully applied to the pharmacokinetic studies of tramadol and ODT in rat brain. Copyright (C) 2017 John Wiley & Sons, Ltd.