Liut Jennifer, Madea Burkhard, Meißner Dirk, Lützen Arne, Javidi Sirous, Hess Cornelius, Krämer Michael
Institute of Forensic Medicine, Forensic Toxicology, University of Bonn, Bonn 53111, Germany.
Kekulé-Institute for Organic Chemistry and Biochemistry, University of Bonn, Bonn 53121, Germany.
J Anal Toxicol. 2025 Feb 15;49(2):73-84. doi: 10.1093/jat/bkae095.
The problem of finding a suitable biomarker to widen the detection window of γ-hydroxybutyric acid (GHB) intake remains a challenge in forensic toxicology. Based on previously published results, the present study deals with the evaluation of a fatty acid ester of GHB (4-palmitoyloxy butyrate [GHB-Pal]) in whole blood as a potential biomarker to extend the detection window of GHB use, e.g. in drug-facilitated sexual assaults. A liquid chromatography-mass spectrometry (LC-MS-MS) method for the quantification of GHB-Pal in whole blood was validated. Whole blood samples were collected from subjects involed in police roadside controls (n = 113) and from narcolepsy patients (n = 10) after the controlled administration of Xyrem® (sodium oxybate). Both sample collectives were previously tested for GHB using two different methods: ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) and gas chromatography-mass spectrometry (GC-MS). In samples from routine police casework, GHB-Pal was detected in 67 out of 113 analysed GHB-positive samples with a mean concentration of 0.8 ng/mL ± 0.5 ng/mL (standard deviation). Among samples that were tested positive for both compounds, no linear correlation was observed between GHB and GHB-Pal concentrations (r = 0.508). In contrast, GHB-Pal was not detected in any of the blood samples analysed from the patients. The absence of GHB and GHB-Pal in the patient cohort may be attributed to the time interval between dose intake and blood collection (approximately 3 and 6 h), during which GHB was eliminated from the body. Furthermore, GHB-Pal was only detectable at a GHB concentration of at least 16 µg/mL, which indicates that endogenous concentrations or low GHB doses may not be sufficient for GHB-Pal formation. Due to missing correlation between both compounds and the lack of GHB-Pal detection several hours after GHB administration, it can be assumed that GHB-Pal in blood is not a suitable biomarker to widen the detection window of GHB.
寻找合适的生物标志物以拓宽γ-羟基丁酸（GHB）摄入检测窗口期的问题，在法医毒理学领域仍是一项挑战。基于先前发表的研究结果，本研究探讨了全血中GHB的脂肪酸酯（4-棕榈酰氧基丁酸酯[GHB-Pal]）作为一种潜在生物标志物，用于延长GHB使用检测窗口期的评估，例如在药物辅助性性侵案件中。验证了一种用于定量全血中GHB-Pal的液相色谱-质谱联用（LC-MS-MS）方法。从参与警方路边检查的受试者（n = 113）以及发作性睡病患者（n = 10）在受控服用羟丁酸钠（Xyrem®）后采集全血样本。这两个样本群体之前都使用两种不同方法检测过GHB：超高效液相色谱-串联质谱联用（UPLC-MS-MS）和气相色谱-质谱联用（GC-MS）。在警方日常办案的样本中，113份经分析为GHB阳性的样本中有67份检测到GHB-Pal，平均浓度为0.8 ng/mL ± 0.5 ng/mL（标准差）。在两种化合物均检测为阳性的样本中，未观察到GHB与GHB-Pal浓度之间存在线性相关性（r = 0.508）。相比之下，在患者的任何一份分析血样中均未检测到GHB-Pal。患者群体中未检测到GHB和GHB-Pal，可能归因于给药与采血之间的时间间隔（约3小时和6小时），在此期间GHB已从体内消除。此外，仅在GHB浓度至少为16 μg/mL时才能检测到GHB-Pal，这表明内源性浓度或低剂量GHB可能不足以形成GHB-Pal。由于两种化合物之间缺乏相关性，且在GHB给药数小时后未检测到GHB-Pal，因此可以推测血液中的GHB-Pal并非拓宽GHB检测窗口期的合适生物标志物。
