首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations
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Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations

机译:使用人肝细胞孵育的吡咯烷基合成阴茎α-PHP和4F-α-PVP代谢物分析

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摘要

For more than ten years, new synthetic cathinones (SCs) mimicking the effects of controlled cocaine-like stimulants have flooded the illegal drug market, causing numerous intoxications and fatalities. There are often no data on the pharmacokinetics of these substances when they first emerge onto the market. However, the detection of SC metabolites is often critical in order to prove consumption in clinical and forensic settings. In this research, the metabolite profile of two pyrrolidinyl SCs, α-pyrrolidinohexaphenone (α-PHP) and 4′′-fluoro-α-pyrrolidinovalerophenone (4F-α-PVP), were characterized to identify optimal intake markers. Experiments were conducted using pooled human hepatocyte incubations followed by liquid chromatography–high-resolution tandem mass spectrometry and data-mining software. We suggest α-PHP dihydroxy-pyrrolidinyl, α-PHP hexanol, α-PHP 2′-keto-pyrrolidinyl-hexanol, and α-PHP 2′-keto-pyrrolidinyl as markers of α-PHP use, and 4F-α-PVP dihydroxy-pyrrolidinyl, 4F-α-PVP hexanol, 4F-α-PVP 2′-keto-pyrrolidinyl-hexanol, and 4F-α-PVP 2′-keto-pyrrolidinyl as markers of 4F-α-PVP use. These results represent the first data available on 4F-α-PVP metabolism. The metabolic fate of α-PHP was previously studied using human liver microsomes and urine samples from α-PHP users. We identified an additional major metabolite (α-PHP dihydroxy-pyrrolidinyl) that might be crucial for documenting exposure to α-PHP. Further experiments with suitable analytical standards, which are yet to be synthesized, and authentic specimens should be conducted to confirm these results.
机译:十多年来,新的合成阴茎(SCS)模仿受控可卡因样刺激剂的影响淹没了非法药物市场,造成了众多毒害和死亡。当他们首次出现在市场上时,这些物质的药代动力学通常没有数据。然而,SC代谢物的检测通常是至关重要的,以便在临床和法医环境中证明消耗。在该研究中,两种吡咯烷基SCS,α-PyrrolidinoHexhenone(α-PHP)和4' - 氟-α-吡咯烷戊二酮(4F-α-PVP)的代谢物曲线特征在于鉴定最佳的进气标记。使用合并的人肝细胞孵育进行实验,然后进行液相色谱 - 高分辨率串联质谱和数据挖掘软件。我们建议α-PHP二羟基 - 吡咯烷基,α-PHP六番醇,α-PHP 2'-酮 - 吡咯烷基 - 己醇和α-PHP 2'-酮 - 吡咯烷基作为α-PHP使用的标志物,和4F-α-PVP二羟基 - 吡咯烷基,4F-α-PVP六番醇,4F-α-PVP 2'-酮 - 吡咯烷基 - 己醇,4F-α-PVP 2'-酮吡咯烷基作为4F-α-PVP使用的标记。这些结果表示在4F-α-PVP代谢上提供的第一个数据。以前使用来自α-PHP用户的人肝微粒体和尿液样品研究α-PHP的代谢命运。我们鉴定了一种额外的主要代谢物(α-PHP二羟基 - 吡咯烷基),其对于记录α-PHP暴露可能是至关重要的。应进行具有合成的合适分析标准的进一步实验,并应进行真实的标本以确认这些结果。

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