Parallel artificial liquid membrane extraction (PALME) is a 96-well plate setup variant of liquid-phase microextraction. Basic or acidic analytes are extracted in neutral form from the sample, through a supported liquid membrane (SLM), and into aqueous acceptor. PALME is already considered a green extraction technique, but in the current conceptual work, we sought to make it even greener by replacing the use of organic solvents with essential oils (EO). PALME was combined with LC-MS/MS for analysis of plasma samples and multiple drugs of abuse with toxicological relevance (amphetamines, phenethylamines, synthetic cathinones, designer benzodiazepines, ayahuasca alkaloids, lysergic acid diethylamide, and ketamine). Fourteen EO were compared to organic solvents frequently used in PALME. The EO termed smart & sassy yielded the best analyte recovery for all drugs studied and was thus selected as SLM. Then, factorial screening and Box-Behnken were employed to optimize the technique. The extraction time, concentration of base, sample volume, and percentage of trioctylamine significantly impacted analyte recovery. The optimum values were defined as 120 min, 10 mmol/L of NaOH, 150 μL, and 0%, respectively. Once optimized, validation parameters were 1–100 ng mL-1 as linear range, accuracy ±16.4%, precision >83%, 1 ng mL-1 as limit of quantitation, 0.1–0.75 ng mL-1 as limit of detection, matrix effect <20%, and recovery 20–106%. Additionally, EO purchased from different production batches were tested and achieved acceptable reproducibility. Data were in compliance with requirements set by internationally accepted validation guidelines and the applicability of the technique was proven using authentic samples. In this study, the use of an EO provided a solvent-free sample preparation technique suited to extract different classes of drugs of abuse from plasma samples, dismissing the use of hazardous organic solvents. The method also provided excellent sample clean-up, thus being a simple and efficient tool for toxicological applications that is in agreement with the principles of sustainable chemistry.

中文翻译：

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使用 LC-MS/MS 无溶剂平行人工液膜萃取血浆样品中的滥用药物

平行人工液膜萃取 (PALME) 是液相微萃取的 96 孔板设置变体。碱性或酸性分析物以中性形式从样品中通过支撑液膜 (SLM) 萃取到水性受体中。 PALME 已被认为是一种绿色提取技术，但在当前的概念工作中，我们试图通过用精油 (EO) 代替有机溶剂的使用来使其更加环保。 PALME 与 LC-MS/MS 相结合，用于分析血浆样本和多种具有毒理学相关性的滥用药物（安非他明、苯乙胺、合成卡西酮、苯二氮卓类药物、死藤水生物碱、麦角酸二乙酰胺和氯胺酮）。将 14 种 EO 与 PALME 中常用的有机溶剂进行了比较。被称为 smart & sassy 的 EO 对所有研究的药物产生了最佳的分析物回收率，因此被选为 SLM。然后，采用因子筛选和 Box-Behnken 来优化该技术。萃取时间、碱浓度、样品体积和三辛胺百分比显着影响分析物回收率。最佳值分别定义为 120 分钟、NaOH 10 mmol/L、150 μL 和 0%。优化后，验证参数为 1–100 ng mL-1 作为线性范围，准确度 ±16.4%，精密度 >83%，1 ng mL-1 作为定量限，0.1–0.75 ng mL-1 作为检测限，矩阵效果<20%，回收率20-106%。此外，对不同生产批次购买的环氧乙烷进行了测试并达到了可接受的再现性。数据符合国际公认的验证指南规定的要求，并且使用真实样品证明了该技术的适用性。在这项研究中，环氧乙烷的使用提供了一种无溶剂样品制备技术，适合从血浆样品中提取不同类别的滥用药物，无需使用有害有机溶剂。该方法还提供了出色的样品净化能力，因此成为符合可持续化学原理的毒理学应用的简单而有效的工具。