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从人血浆中对酸性药物进行彻底且稳定的电膜萃取。

Exhaustive and stable electromembrane extraction of acidic drugs from human plasma.

作者信息

Huang Chuixiu, Gjelstad Astrid, Seip Knut Fredrik, Jensen Henrik, Pedersen-Bjergaard Stig

机构信息

School of Pharmacy, University of Oslo, PO Box 1068, Blindern, Oslo 0316, Norway; G&T Septech AS, PO Box 33, Ytre Enebakk 1917, Norway.

School of Pharmacy, University of Oslo, PO Box 1068, Blindern, Oslo 0316, Norway.

出版信息

J Chromatogr A. 2015 Dec 18;1425:81-7. doi: 10.1016/j.chroma.2015.11.052. Epub 2015 Nov 19.

DOI:10.1016/j.chroma.2015.11.052
PMID:26632516
Abstract

The first part of the current work systematically described the screening of different types of organic solvents as the supported liquid membrane (SLM) for electromembrane extraction (EME) of acidic drugs, including different alcohols, ketones, and ethers. Seven acidic drugs with a wide logP range (1.01-4.39) were selected as model substances. For the first time, the EME recovery of acidic drugs and system-current across the SLM with each organic solvent as SLM were investigated and correlated to relevant solvent properties such as viscosity and Kamlet and Taft solvatochromic parameters. Solvents with high hydrogen bonding acidity (α) and dipolarity-polarizability (π*) were found to be successful SLMs, and 1-heptanol was the most efficient candidate, which provided EME recovery in the range of 94-110%. Both hydrogen bonding interactions, dipole-dipole interactions, and hydrophobic interactions were involved in stabilizing the deprotonated acidic analytes (with high hydrogen bonding basicity and high dipole moment) during mass transfer across the SLM. The efficiency of the extraction normally decreased with increasing hydrocarbon chain length of the SLM, which was mainly due to increasing viscosity and decreasing α and π* values. The system-current during EME was found to be dependent on the type and the volume of the SLM. In contact with human plasma, an SLM of pure 1-heptanol was unstable, and to improve stability, 1-heptanol was mixed with 2-nitrophenyl octyl ether (NPOE). With this SLM, exhaustive EME was performed from diluted human plasma, and the recoveries of five out of seven analytes were over 91% after 10min EME. This approach was evaluated using HPLC-UV, and the evaluation data were found to be satisfactory.

摘要

当前工作的第一部分系统地描述了筛选不同类型的有机溶剂作为支撑液膜(SLM)用于酸性药物的电膜萃取(EME),包括不同的醇类、酮类和醚类。选择了七种logP范围较宽(1.01 - 4.39)的酸性药物作为模型物质。首次研究了以每种有机溶剂作为支撑液膜时,酸性药物的EME回收率和跨支撑液膜的系统电流,并将其与相关溶剂性质(如粘度以及Kamlet和Taft溶剂化显色参数)相关联。发现具有高氢键酸度(α)和偶极-极化率(π*)的溶剂是成功的支撑液膜,1-庚醇是最有效的候选物,其EME回收率在94 - 110%范围内。在跨支撑液膜的传质过程中,氢键相互作用、偶极-偶极相互作用和疏水相互作用都参与了稳定去质子化的酸性分析物(具有高氢键碱度和高偶极矩)。萃取效率通常随着支撑液膜碳氢链长度的增加而降低,这主要是由于粘度增加以及α和π*值降低。发现EME过程中的系统电流取决于支撑液膜的类型和体积。与人体血浆接触时,纯1-庚醇的支撑液膜不稳定,为提高稳定性,将1-庚醇与2-硝基苯基辛基醚(NPOE)混合。使用这种支撑液膜,从稀释的人体血浆中进行了完全EME,10分钟EME后七种分析物中有五种的回收率超过91%。使用高效液相色谱-紫外检测法对该方法进行了评估,评估数据令人满意。

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