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导电小瓶电膜萃取法从唾液中提取阿片类药物。

Conductive vial electromembrane extraction of opioids from oral fluid.

机构信息

Department of Clinical Pharmacology, St. Olav University Hospital, Professor Brochs Gate 6, 7030, Trondheim, Norway.

Department of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316, Oslo, Norway.

出版信息

Anal Bioanal Chem. 2023 Sep;415(22):5323-5335. doi: 10.1007/s00216-023-04807-3. Epub 2023 Jun 29.

Abstract

The use of oral fluid as sample matrix has gained significance in the analysis of drugs of abuse due to its non-invasive nature. In this study, the 13 opioids morphine, oxycodone, codeine, O-desmethyl tramadol, ethylmorphine, tramadol, pethidine, ketobemidone, buprenorphine, fentanyl, cyclopropylfentanyl, etonitazepyne, and methadone were extracted from oral fluid using electromembrane extraction based on conductive vials prior to analysis with ultra-high performance liquid chromatography-tandem mass spectrometry. Oral fluid was collected using Quantisal collection kits. By applying voltage, target analytes were extracted from oral fluid samples diluted with 0.1% formic acid, across a liquid membrane and into a 300 μL 0.1% (v/v) formic acid solution. The liquid membrane comprised 8 μL membrane solvent immobilized in the pores of a flat porous polypropylene membrane. The membrane solvent was a mixture of 6-methylcoumarin, thymol, and 2-nitrophenyloctyl ether. The composition of the membrane solvent was found to be the most important parameter to achieve simultaneous extraction of all target opioids, which had predicted log P values in the range from 0.7 to 5.0. The method was validated in accordance to the guidelines by the European Medical Agency with satisfactory results. Intra- and inter-day precision and bias were within guideline limits of ± 15% for 12 of 13 compounds. Extraction recoveries ranged from 39 to 104% (CV ≤ 23%). Internal standard normalized matrix effects were in the range from 88 to 103% (CV ≤ 5%). Quantitative results of authentic oral fluid samples were in accordance with a routine screening method, and external quality control samples for both hydrophilic and lipophilic compounds were within acceptable limits.

摘要

唾液作为样本基质在滥用药物分析中具有重要意义,因为它具有非侵入性。在这项研究中,采用基于导电小瓶的电膜萃取法从唾液中提取了 13 种阿片类药物(吗啡、羟考酮、可待因、O-去甲曲马多、乙基吗啡、曲马多、哌替啶、酮苯丙胺、丁丙诺啡、芬太尼、环丙基芬太尼、依他尼酮和美沙酮),然后用超高效液相色谱-串联质谱法进行分析。采用 Quantisal 采集试剂盒采集唾液。通过施加电压,将目标分析物从用 0.1%甲酸稀释的唾液样品中萃取出来,穿过液膜进入 300 μL 0.1%(v/v)甲酸溶液中。液膜由 8 μL 固定在扁平多孔聚丙烯膜孔中的膜溶剂组成。膜溶剂是 6-甲基香豆素、百里香酚和 2-硝基苯辛醚的混合物。结果发现,膜溶剂的组成是实现同时提取所有目标阿片类药物的最重要参数,这些药物的预测 log P 值在 0.7 到 5.0 之间。该方法按照欧洲药品管理局的指南进行了验证,结果令人满意。对于 13 种化合物中的 12 种,日内和日间精密度和偏差均在 ±15%的指南限值内。萃取回收率在 39%至 104%之间(CV ≤ 23%)。内标归一化基质效应在 88%至 103%(CV ≤ 5%)范围内。真实唾液样本的定量结果与常规筛选方法一致,亲水和亲脂性化合物的外部质量控制样本均在可接受范围内。

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