The aim of antidepressant therapy is to induce remission and prevent relapses of major depressive disorder with minimum adverse effects during the treatment. Due to high variability in metabolism, therapeutic drug monitoring is recommended as a useful tool for individualisation of the therapy. For this purpose, we have developed simple and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for quantification of fluoxetine (FLX), venlafaxine (VEN), vortioxetine (VTX) and their active metabolites norfluoxetine (NFLX) and O-desmethylvenlafaxine (ODV). After one-step extraction procedure using OSTRO plate, analytes were separated by gradient elution on Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column with runtime 4.2 min. The detection was done on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode with transitions at m/z 310.23 → 148.20 for FLX, m/z 296.23 → 134.20 for NFLX, m/z 278.31 → 121.13 for VEN, m/z 264.31 → 107.14 for ODV and m/z 299.19 → 150.05 for VTX using a positive electrospray ionisation interface. The method was successfully validated according to the European Medicine Agency guideline for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability over a concentration range of 1-300 ng/mL for FLX, NFLX, VEN, ODV and 0.2-100 ng/mL VTX. Extraction recovery for each analyte was > 80 %, and no significant matrix effects were observed. The developed method was employed for quantification of antidepressants in clinical samples from patients treated with either FLX, VEN, or VTX.

中文翻译：

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使用一步样品制备程序通过LC-MS / MS同时测定人血浆中的氟西汀，文拉法辛，伏替西汀及其活性代谢物。

抗抑郁治疗的目的是诱导缓解并预防重度抑郁症复发，同时在治疗期间将不良反应降至最低。由于新陈代谢的高度可变性，建议将治疗药物监测作为个性化治疗的有用工具。为此，我们开发了简单灵敏的超高效液相色谱-串联质谱（UHPLC-MS / MS）方法定量氟西汀（FLX），文拉法辛（VEN），伏替西汀（VTX）及其活性代谢物诺氟西汀（NFLX）和O-去甲基文拉法辛（ODV）。使用OSTRO板进行一步萃取后，通过在Acquity UPLC BEH C18（50×2.1 mm，1.7μm）色谱柱上进行梯度洗脱来分离分析物，运行时间为4.2分钟。通过多反应监测（MRM）模式在三重四极杆串联质谱仪上进行检测，其中FLX的跃迁为m / z 310.23→148.20，NFLX的跃迁为m / z 296.23→134.20，VEN，m的跃迁为m / z 278.31→121.13使用正电喷雾电离界面，对于ODV为/ z 264.31→107.14，对于VTX为m / z 299.19→150.05。该方法已根据欧洲药物管理局的指南成功验证，在1-300 ng / mL的浓度范围内具有选择性，线性和检测下限，精密度和准确性，基质效应，提取回收率，残留，稀释完整性和稳定性用于FLX，NFLX，VEN，ODV和0.2-100 ng / mL VTX。每种分析物的提取回收率> 80％，并且未观察到明显的基质效应。