In this study, a specific and quick ultra‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was fully developed and validated for simultaneous measurement of the rat plasma levels of vortioxetine (VOR), Lu AA34443 (the major metabolite of VOR), fluoxetine and its metabolite norfluoxetine with diazepam as the internal standard (IS). After a simple protein precipitation with acetonitrile for sample preparation, the separation of the analytes were performed on an Acquity UPLC BEH C18 (2.1 × 50 mm, 1.7 μm) column, with acetonitrile and 0.1% formic acid in water as mobile phase by gradient elution. The detection was achieved on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode via an electrospray ionization source. Good linearity was observed in the calibration curve for each analyte. The data of precision, accuracy, matrix effect, recovery and stability all conformed to the bioanalytical method validation of acceptance criteria of US Food and Drug Administration recommendations. The newly developed UPLC–MS/MS method allowed simultaneous quantification of VOR, fluoxetine and their metabolites for the first time and was successfully applied to a pharmacokinetic study in rats.

中文翻译：

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通过UPLC-MS / MS同时定量大鼠血浆中的vortioxetine，fluoxetine及其代谢物。

在这项研究中，完全开发出了一种快速特异的快速高效液相色谱串联质谱（UPLC–MS / MS）方法，并验证了该方法可同时测量大鼠血浆中的伏替西汀（VOR），鲁AA34443（主要代谢产物VOR），氟西汀及其代谢物去氟西汀（以地西az为内标（IS））。用乙腈进行简单的蛋白质沉淀以制备样品后，在Acquity UPLC BEH C18（2.1×50 mm，1.7μm）色谱柱上进行分析物的分离，采用乙腈和0.1％的甲酸水溶液作为流动相，通过梯度洗脱。该检测是在三重四极串联质谱仪上通过电喷雾电离源通过多重反应监测模式实现的。在每种分析物的校准曲线中均观察到良好的线性。精密度，准确度，基质效应，回收率和稳定性数据均符合美国食品药品监督管理局建议的接受标准的生物分析方法验证。新开发的UPLC-MS / MS方法首次实现了VOR，氟西汀及其代谢物的同时定量，并成功地应用于大鼠的药代动力学研究。