de Castro A, Concheiro M, Quintela O, Cruz A, López-Rivadulla M
Forensic Toxicology Service, Institute of Legal Medicine of the University of Santiago de Compostela, C/San Francisco s/n, 15782 Santiago de Compostela, Spain.
J Pharm Biomed Anal. 2008 Sep 10;48(1):183-93. doi: 10.1016/j.jpba.2008.05.024. Epub 2008 May 28.
In this paper, a fast, sensitive and selective LC-MS/MS method is described for the simultaneous determination of amitriptyline, imipramine, clomipramine, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and venlafaxine, as well as some of their main metabolites (nortriptyline, desipramine, norclomipramine and norfluoxetine), in oral fluid and plasma. The sample (0.2 mL) was extracted with an automated solid-phase extraction system (ASPEC XL), using mixed mode OASIS MCX cartridges. Chromatographic separation was performed in a Sunfire C18 IS column (20 mmx2.1 mm, 3.5 microm), using a gradient of acetonitrile and ammonium formate (pH 3; 2 mM) as mobile phase, which allowed the elution of all the compounds in less than 5 min. The method has been fully validated in both specimens. This method was initially applied to the analysis of oral fluid and plasma samples from patients on antidepressant treatment in order to assess for which compounds it was likely to find a good correlation between both matrices. The best results were obtained for venlafaxine, so the study was extended for this compound, comparing the ratio between oral fluid and plasma concentrations (ROF/PL) in five patients on venlafaxine treatment when both samples were collected simultaneously on four different occasions. An important inter and intraindividual variability was found in oral fluid concentrations for 150 mg dose (mean=287.5 ng/m, range 58.8-531.2 ng/mL) and for 75 mg dose (mean=186.3 ng/mL, range=82.1-289.2 ng/mL). R(OF/PL) was calculated for each patient on the four different occasions, showing also a high variability (CV=24.2-69.6%).
本文描述了一种快速、灵敏且具选择性的液相色谱-串联质谱法，用于同时测定口腔液和血浆中的阿米替林、丙咪嗪、氯米帕明、氟西汀、帕罗西汀、舍曲林、氟伏沙明、西酞普兰和文拉法辛，以及它们的一些主要代谢物（去甲替林、地昔帕明、去甲氯米帕明和去甲氟西汀）。取0.2 mL样品，使用混合型OASIS MCX柱，通过自动固相萃取系统（ASPEC XL）进行萃取。在Sunfire C18 IS柱（20 mm×2.1 mm，3.5 µm）上进行色谱分离，以乙腈和甲酸铵（pH 3；2 mM）的梯度溶液作为流动相，可在不到5分钟内洗脱所有化合物。该方法已在两种样本中得到充分验证。此方法最初应用于分析接受抗抑郁治疗患者的口腔液和血浆样本，以评估哪些化合物在两种基质之间可能具有良好的相关性。文拉法辛获得了最佳结果，因此针对该化合物扩展了研究范围，比较了五名接受文拉法辛治疗的患者在四个不同时间点同时采集口腔液和血浆样本时口腔液与血浆浓度之比（ROF/PL）。发现150 mg剂量（均值 = 287.5 ng/mL，范围58.8 - 531.2 ng/mL）和75 mg剂量（均值 = 186.3 ng/mL，范围 = 82.1 - 289.2 ng/mL）的口腔液浓度存在显著的个体间和个体内变异性。计算了每位患者在四个不同时间点的R(OF/PL)，结果也显示出高度变异性（CV = 24.2 - 69.6%）。
