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 200F, 3001 Leuven, Belgium.
Talanta. 2018 Jul 1;184:369-374. doi: 10.1016/j.talanta.2018.03.001. Epub 2018 Mar 6.
Ionic liquids (ILs) are becoming a trending topic in sample preparation technology, due to their low volatility, low flammability and tunable physiochemical properties. The latter affords the opportunity for creating task-specific solvents. In toxicology, these tailored ILs were not introduced yet; however, they can be significant for drug extraction purposes. This study screens 11 commercially available ILs as potential extraction media for benzodiazepines from blood samples via liquid-liquid microextraction, coupled to liquid chromatography - tandem mass spectrometry (LC-MS/MS). Structure-extraction relationships were deducted from recovery and matrix effect results (n = 5), allowing us to devise some of the favorable features in a tailored IL for benzodiazepine extraction. Overall, long alkyl chains are to be avoided, as they may sterically hinder desirable π-stacking interactions. For the same reason, aromatic planar cations, as imidazolium and pyridinium, were more effective in comparison with ammonium and pyrrolidinium. Furthermore, viscosity negatively impacted both recoveries and matrix effects. High viscosities limited mass transfer during dispersion and impeded electrospray ionization processes. In conclusion, this study evaluates which physicochemical features an IL should possess to efficiently extract benzodiazepines from whole blood.
离子液体（ILs）由于其低挥发性、低可燃性和可调节的物理化学性质，在样品制备技术中成为一个热门话题。后者为创建特定于任务的溶剂提供了机会。在毒理学中，这些定制的 IL 尚未被引入，但它们可能对药物提取很重要。本研究通过液液微萃取，将 11 种市售 IL 作为从血液样本中提取苯并二氮䓬类药物的潜在萃取介质进行筛选，与液相色谱-串联质谱（LC-MS/MS）联用。从回收率和基质效应结果中推断出结构-萃取关系（n=5），使我们能够设计出一种用于苯并二氮䓬类药物萃取的定制 IL 的一些有利特征。总的来说，应避免长烷基链，因为它们可能会阻碍所需的π-堆积相互作用。出于同样的原因，与铵和吡咯烷相比，芳香平面阳离子（如咪唑𬭩和吡啶𬭩）在萃取苯并二氮䓬类药物方面更有效。此外，粘度会对回收率和基质效应产生负面影响。高粘度会限制分散过程中的传质，并阻碍电喷雾电离过程。总之，本研究评估了 IL 应该具有哪些物理化学性质才能从全血中有效地提取苯并二氮䓬类药物。
