Synthetic drugs for recreational purposes are in constant evolution, and their consumption promotes a significant increase in intoxication cases, resulting in damaging public health. The development of analytical methodologies to confirm the consumption of illicit drugs in biological matrices is required for the control of these substances. This work exploited the development of an extraction method based on homogenous liquid–liquid microextraction with switchable hydrophilicity solvent (SHS) as extraction phase for the determination of the synthetic drugs 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine and N-methoxybenzyl-methoxyphenylethylamine derivates (25B, 25C and 25I) in postmortem blood, followed by liquid chromatography coupled to mass spectrometry in tandem. The optimized sample preparation conditions consisted of using 250 µL of ZnSO4 10% and 50 µL of NaOH 1 mol/L in the protein precipitation step; N,N-dimethylcyclohexylamine was used as SHS, 650 μL of a mixture of SHS:HCl 6 mol/L (1:1 v/v), 500 μL of whole blood, 500 μL of NaOH 10 mol/L and 1 min of extraction time. The proposed method was validated, providing determination coefficients higher than 0.99 for all analytes; limit of detection and limit of quantitation ranged from 0.1 to 10 ng/mL; intra-run precision from 2.16% to 9.19%; inter-run precision from 2.39% to 9.59%; bias from 93.57% to 115.71% and matrix effects from 28.94% to 51.54%. The developed method was successfully applied to four authentic postmortem blood samples from synthetic drugs users, and it was found to be reliable with good selectivity.

中文翻译：

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可切换亲水性溶剂均相液-液微萃取在测定死后血样中 MDMA、MDA 和 NBOMe 中的应用

用于娱乐目的的合成药物在不断发展，其消费促进了中毒病例的显着增加，从而损害了公众健康。为了控制这些物质，需要开发分析方法来确认生物基质中非法药物的消费情况。本工作开发了一种基于均相液-液微萃取的萃取方法，以可切换亲水性溶剂 (SHS) 作为萃取相，用于测定合成药物 3,4-亚甲基二氧基甲基苯丙胺、3,4-亚甲基二氧基苯丙胺和 N-甲氧基苄基-甲氧基苯乙胺死后血液中的衍生物（25B、25C 和 25I），然后进行液相色谱与质谱联用。优化的样品制备条件包括在蛋白质沉淀步骤中使用 250 µL ZnSO4 10% 和 50 µL NaOH 1 mol/L；N,N-二甲基环己胺用作 SHS，650 μL SHS:HCl 6 mol/L (1:1 v/v) 的混合物，500 μL 全血，500 μL NaOH 10 mol/L 和 1 min提取时间。所提出的方法经过验证，所有分析物的测定系数均高于 0.99；检测限和定量限为 0.1 至 10 ng/mL；运行内精确度从 2.16% 提高到 9.19%；批间精度从 2.39% 提高到 9.59%；偏差从 93.57% 到 115.71%，基质效应从 28.94% 到 51.54%。所开发的方法成功地应用于来自合成药物使用者的四个真实的死后血液样本，发现该方法可靠且选择性好。