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Methyl-4-hydroxybutyrate and Ethyl-4-hydroxybutyrate as Potential Markers for Simultaneous Consumption of GHB/GBL and Alcohol: Preliminary Investigations.
Journal of Analytical Toxicology ( IF 2.3 ) Pub Date : 2020-08-11 , DOI: 10.1093/jat/bkaa096
Theresa Küting 1 , Niklas Beier 1 , Michael Krämer 1 , Burkhard Madea 1
Affiliation  

Abstract
γ-Hydroxybutyric acid (GHB) and its corresponding lactone γ-butyrolactone (GBL) are misused as knock out (k.o.) drugs. The short detection window and the major inter- and intra-individual variations of endogenous GHB concentrations in commonly used matrices such as blood and urine complicate the analytical proof of an exogenous GHB/GBL administration. We searched for an alternative way to prove an exogenous GHB/GBL administration via detection of methyl- and ethyl-4-hydroxybutyrate, which could arise in alcoholic solutions after spiking with GHB/GBL. A liquid chromatographic–triple quadrupole mass spectrometric method was developed and validated to quantitatively determine methyl- and ethyl-4-hydroxybutyrate in alcoholic beverages (limit of detection [LoD]: 5.8 and 3.4 ng/mL, respectively). A sample collective of alcoholic beverages (n = 47) revealed natural occurring amounts of ethyl-4-hydroxybutyrate (<LoD—approx. 3980 ng/mL) with higher concentrations particularly found in wine samples. Nearly no ethyl-4-hydroxybutyrate was observable in spirits/liqueurs and no methyl-4-hydroxybutyrate was detectable at all. A moderate correlation was shown between the ethyl-4-hydroxybutyrate concentration and the pH-value in wine samples (pH 2.9–3.7, n = 29) as well as between the ethyl-4-hydroxybutyrate concentration and the GHB concentration in all measured beverages (GHB: < limit of quantification [LoQ]—11.4 µg/mL, n = 47). A dependency on alcohol content could not be observed. A voluntary intake (n = 1) of 750-mL wine naturally containing high amounts of ethyl-4-hydroxybutyrate (approx. 2010 ng/mL) revealed no observable GHB-ester concentrations in blood and urine. Furthermore, an experiment simulating a beverage that could potentially be used in a drug-facilitated crime (DFC) case showed ethyl-4-hydroxybutyrate concentrations exceeding the concentrations naturally observed in beverage samples. However, in order to evaluate whether ethyl-4-hydroxybutyrate could be useful as marker for the co-consumption of GHB/GBL and alcohol and to prolong the detection window of unintended GHB/GBL intake, further experiments have to be performed.


中文翻译:

4-羟丁酸甲酯和4-羟丁酸乙酯是同时消费GHB / GBL和酒精的潜在标志物:初步研究。

摘要
γ-羟基丁酸(GHB)及其相应的内酯γ-丁内酯(GBL)被误用作敲除(ko)药物。常用基质(例如血液和尿液)中内源性GHB浓度的检测窗口短以及个体间和个体内的主要个体差异使外源性GHB / GBL给药的分析证据复杂化。我们搜索了另一种方法,可通过检测甲基和4-羟基丁酸乙酯来证明外源性GHB / GBL的施用,当与GHB / GBL掺和后,可能会在酒精溶液中产生。液相色谱-三重四极杆质谱法得到了发展,并经过验证可定量测定酒精饮料中的4-羟基丁酸甲酯和4-羟基丁酸乙酯(检出限[LoD]:分别为5.8和3.4 ng / mL)。一组酒精饮料样品(n = 47)显示出自然产生的4-羟基丁酸乙酯(<LoD-约3980 ng / mL)的自然含量,尤其是在葡萄酒样品中浓度更高。在烈酒/甜酒中几乎没有观察到4-羟基丁酸乙酯,根本没有检测到4-羟基丁酸甲酯。葡萄酒样品中4-羟基丁酸乙酯的浓度与pH值(pH 2.9-3.7,n = 29)之间以及所有测量饮料中-4-羟基丁酸乙酯的浓度与GHB浓度之间存在适度的相关性。 (GHB:<定量极限[LoQ]-11.4 µg / mL,n = 47)。无法观察到对酒精含量的依赖性。自愿摄入(n = 1)的750毫升葡萄酒,其中自然含有大量的4-羟基丁酸乙酯 2010 ng / mL)显示血液和尿液中没有可观察到的GHB-酯浓度。此外,一项模拟可能在毒品犯罪(DFC)案件中使用的饮料的实验表明,4-羟基丁酸乙酯的浓度超过了饮料样品中自然观察到的浓度。但是,为了评估4-羟基丁酸乙酯是否可以用作共同摄入GHB / GBL和酒精的标记,并延长意外摄入的GHB / GBL的检测时间,必须进行进一步的实验。
更新日期:2020-12-12
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