Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven (KU Leuven), Campus Gasthuisberg, O&N II, P.O. Box 922, Herestraat 49, 3000 Leuven, Belgium.
Molecular Design and Synthesis, Department of Chemistry, University of Leuven (KU Leuven), Campus Arenberg, P.O. Box 2404, Celestijnenlaan 200 F, 3001 Leuven, Belgium.
Talanta. 2018 Apr 1;180:292-299. doi: 10.1016/j.talanta.2017.12.044. Epub 2017 Dec 16.
This study aims to prove that ionic liquids (ILs) can be used as extraction solvents in a liquid-liquid microextraction, coupled to LC-MS/MS, for the quantification of a large group of antidepressants in whole blood samples. The sample preparation procedure consisted of adding 1.0mL aqueous buffer pH 3.0 and 60µL of IL (1-butyl-3-methylimidazolium hexafluorophosphate) to 1.0mL whole blood. Subsequently, a 5-min rotary mixing step was performed followed by centrifugation. The lower IL phase was collected, diluted 1:10 in methanol and 10µL was injected into the LC-MS/MS. The following analytes were included in the full-quantitative method: agomelatine, amitriptyline, bupropion, clomipramine, dosulepin, doxepin, duloxetine, escitalopram, fluoxetine, imipramine, maprotiline, mianserin, mirtazapine, nortriptyline, paroxetine, reboxetine, trazodone and venlafaxine. Selectivity was checked for 10 different whole blood matrices. Additionally, possible interferences of deuterated standards or other antidepressants were evaluated. Overall, no interferences were found. For each analyte a matrix-matched calibration curve was constructed (7 levels, n = 6), covering therapeutic and low toxic concentrations. Accuracy and precision were evaluated over eight days, at three concentration levels (n = 2). Bias, repeatability and intermediate precision results met with the proposed validation criteria, except for fluvoxamine, which was therefore only included in the semi-quantitative method. LOQs were set at the lowest calibrator concentration and LOD values were - for most analytes - within a range of 1-2ng/mL. Recoveries (RE) and matrix effects (ME) were evaluated for five types of donor whole blood, at two concentration levels. RE values were within a range of 53.11-132.98%. ME values were within a range of 61.92-123.24%. In conclusion, this study proves the applicability of ILs as extraction solvents for a large group of antidepressants in complex whole blood matrices.
本研究旨在证明离子液体（ILs）可用于液相微萃取中的萃取溶剂，并与 LC-MS/MS 联用，对全血样品中的一大类抗抑郁药进行定量分析。样品制备过程包括向 1.0mL 水性缓冲液 pH 3.0 中加入 60µL IL（1-丁基-3-甲基咪唑六氟磷酸盐），然后加入 1.0mL 全血。随后进行 5 分钟的旋转混合步骤，然后进行离心。收集下层 IL 相，用甲醇稀释 1:10，取 10µL 注入 LC-MS/MS。以下分析物包括在全定量方法中：阿戈美拉汀、阿米替林、安非他酮、氯米帕明、多塞平、多塞平、度洛西汀、依西酞普兰、氟西汀、丙咪嗪、马普替林、米氮平、米那普仑、去甲替林、帕罗西汀、雷贝拉唑、曲唑酮和文拉法辛。对 10 种不同的全血基质进行了选择性检查。此外，还评估了氘代标准品或其他抗抑郁药可能的干扰。总的来说，没有发现干扰。对于每个分析物，都构建了基质匹配校准曲线（7 个水平，n = 6），涵盖治疗和低毒性浓度。在 8 天内，在 3 个浓度水平（n = 2）上评估了准确性和精密度。偏差、重复性和中间精密度结果符合提出的验证标准，但氟伏沙明除外，因此仅包括在半定量方法中。LOQ 设置在最低校准器浓度，LOD 值 - 对于大多数分析物 - 在 1-2ng/mL 的范围内。在两个浓度水平下，对五种类型的供体全血评估了回收率（RE）和基质效应（ME）。RE 值在 53.11-132.98%的范围内。ME 值在 61.92-123.24%的范围内。总之，本研究证明了离子液体作为萃取溶剂在复杂全血基质中对一大类抗抑郁药的适用性。
