Hansen Frederik André, Santigosa-Murillo Elia, Ramos-Payán Maria, Muñoz María, Leere Øiestad Elisabeth, Pedersen-Bjergaard Stig
Department of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316, Oslo, Norway.
Department of Analytical Chemistry, Universitat Autónoma de Barcelona, 08193, Bellaterra, Barcelona, Spain.
Anal Chim Acta. 2021 Jan 25;1143:109-116. doi: 10.1016/j.aca.2020.11.044. Epub 2020 Nov 30.
In this work, we investigated for the first time hydrophobic deep eutectic solvents (DES) as supported liquid membrane (SLM) for electromembrane extraction (EME). Camphor, coumarin, DL-menthol, and thymol were used as non-ionic DES components. Different DESs compositions were tested, to study systematically the importance of hydrogen bonding and dispersion/aromatic interactions during mass transfer across the SLM. Unexpectedly, mixtures of coumarin and thymol were highly efficient SLMs, and provided exhaustive or near-exhaustive extraction of non-polar bases, non-polar acids, and polar bases. SLMs with such performance for both bases and acids, in a large polarity window, are not found in current literature. The SLMs were highly aromatic, very strong hydrogen bonding donors, and moderately strong hydrogen bonding acceptors. Aromatic (π type) interactions were apparently very important for transfer of bases, while hydrogen bonding were dominant for acids. EME of six polar basic drugs from plasma, with a coumarin and thymol mixture as SLM, and combined with UHPLC-MS/MS analysis, was evaluated to test the potential for analytical applications. Plasma was diluted 1:1 with phosphate buffer pH 2.0. Calibration curves were linear in the therapeutic ranges (0.970 < R < 0.999), recoveries ranged between 47 and 93%, and repeatability was within 1.6-10.7% RSD. The clean-up efficiency was excellent and no matrix effects from plasma were seen. Presence of trace levels of coumarin in the acceptor phase was however found to cause some ion enhancement. Based on the current work, we foresee more research on the use of DES in EME.
在本研究中，我们首次研究了疏水性深共熔溶剂（DES）作为支撑液膜（SLM）用于电膜萃取（EME）。樟脑、香豆素、DL-薄荷醇和百里酚用作非离子DES组分。测试了不同的DES组成，以系统研究传质过程中氢键以及色散/芳香相互作用在支撑液膜中的重要性。出乎意料的是，香豆素和百里酚的混合物是高效的支撑液膜，能对非极性碱、非极性酸和极性碱进行完全或接近完全的萃取。在当前文献中未发现具有如此酸碱性能且极性范围大的支撑液膜。这些支撑液膜具有高芳香性、极强的氢键供体以及中等强度的氢键受体。芳香（π型）相互作用对碱的传输显然非常重要，而氢键对酸的传输起主导作用。以香豆素和百里酚混合物作为支撑液膜，结合超高效液相色谱-串联质谱（UHPLC-MS/MS）分析，评估了从血浆中萃取六种极性碱性药物的电膜萃取，以测试其分析应用潜力。血浆用pH 2.0的磷酸盐缓冲液1:1稀释。校准曲线在治疗范围内呈线性（0.970 < R < 0.999），回收率在47%至93%之间，重复性的相对标准偏差（RSD）在1.6 - 10.7%以内。净化效率极佳，未观察到血浆的基质效应。然而，发现接受相中痕量香豆素的存在会导致一些离子增强。基于目前的工作，我们预计会有更多关于DES在电膜萃取中应用的研究。
