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检测血漿和尿液中的 γ-羥丁酸相關酸:延長外源性 γ-羥丁酸攝入的檢測窗?

Detection of γ-hydroxybutyric acid-related acids in blood plasma and urine: Extending the detection window of an exogenous γ-hydroxybutyric acid intake?

机构信息

Institute of Forensic Medicine, University of Bonn, Bonn, Germany.

Medical University Innsbruck, University Hospital for Neurology, Innsbruck, Austria.

出版信息

Drug Test Anal. 2021 Sep;13(9):1635-1649. doi: 10.1002/dta.3097. Epub 2021 May 29.

Abstract

In crimes facilitated by γ-hydroxybutyric acid (GHB) administration, the frequent occurrence of anterograde amnesia of the victims as well as the short detection window and variations of endogenous GHB concentrations complicate obtaining analytical proof of GHB administration. Because elevated endogenous organic acid concentrations have been found in the urine of patients with succinic semialdehyde deficiency (leading to accumulation of GHB in human specimens) and after GHB ingestion, we searched for an alternative way to prove GHB administration via detection of elevated organic acid concentrations in blood plasma and urine. We collected blood and urine samples from narcolepsy patients (n = 5) treated with pharmaceuticals containing GHB sodium salt (1.86-3.72 g GHB as free acid per dose). Although GHB was detectable only up to 4 h in concentrations greater than the commonly used cutoff levels in blood plasma, 3,4-dihydroxybutyric acid (3,4-DHB) could be detected up to 12 h in blood plasma in concentrations exceeding initial concentrations of the same patient before GHB ingestion. Furthermore, four of the five patients showed an increase above endogenous levels described in the scientific literature. In urine, GHB concentrations above commonly used cutoff levels could be observed 4.5-9.5 h after GHB intake. Creatinine standardized initial concentrations were reached again for glycolic acid (GA), 3,4-DHB, and 2,4-dihydroxybutyric (2,4-DHB) acid at 6.5-22, 11.5-22, and 8.5-70 h after GHB intake, respectively. Therefore, 2,4-DHB, 3,4-DHB, and GA are promising and should be further investigated as potential biomarkers to prolong the detection window of GHB intake.

摘要

在γ-羟基丁酸(GHB)给药促成的犯罪中,由于受害者经常出现顺行性遗忘,以及内源性 GHB 浓度的检测窗口短且变化,使得获得 GHB 给药的分析证据变得复杂。因为在琥珀酸半醛缺乏症(导致 GHB 在人体标本中积累)患者的尿液中和 GHB 摄入后,发现内源性有机酸浓度升高,我们寻找了一种替代方法,通过检测血浆和尿液中升高的有机酸浓度来证明 GHB 给药。我们从接受含有 GHB 钠盐(每剂 1.86-3.72g GHB 游离酸)药物治疗的发作性睡病患者中收集了血液和尿液样本(n=5)。尽管 GHB 在血浆中的浓度大于常用截止值时只能检测到 4 小时,但在 GHB 摄入前,血浆中 3,4-二羟基丁酸(3,4-DHB)的浓度可检测到 12 小时,超过同一患者的初始浓度。此外,五名患者中的四名显示出高于文献中描述的内源性水平的升高。在尿液中,GHB 浓度高于常用截止值可在 GHB 摄入后 4.5-9.5 小时观察到。在 GHB 摄入后 6.5-22、11.5-22 和 8.5-70 小时,分别达到了甘醇酸(GA)、3,4-DHB 和 2,4-二羟基丁酸(2,4-DHB)酸的肌酐标准化初始浓度。因此,2,4-DHB、3,4-DHB 和 GA 是有前途的,应该进一步研究作为延长 GHB 摄入检测窗口的潜在生物标志物。

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