Dumitrascu Catalina, Iturrospe Elias, Scheir Els, Timmermans Patrick, Fransen Erik, Van Puymbroeck Matthias, Van Nieuwenhove Glenn, Busschots Maryline, D'Hondt Diona, Van Goethem Alexia, Claeys Wout, Van Rafelghem Babette, Baetens Eline, Jorens Philippe G, Gys Celine, Jacobs Werner, Neels Hugo, Covaci Adrian, van Nuijs Alexander L N
Toxicological Centre, University of Antwerp, Antwerp, Belgium.
Department of Laboratory Medicine, Antwerp University Hospital, Edegem, Belgium.
Drug Test Anal. 2025 Aug 4. doi: 10.1002/dta.3937.
Alcohol consumption is widespread worldwide and a leading cause of injuries, morbidity, and mortality. Accurately detecting alcohol use with reliable biomarkers is crucial in clinical and forensic settings. Direct alcohol biomarkers, i.e., ethanol (EtOH), ethyl glucuronide (EtG), ethyl sulphate (EtS), phosphatidylethanol 16:0/18:1 (PEth) reflect short- and long-term consumption. Nevertheless, complementary biomarkers with improved specificity and sensitivity are needed to better assess alcohol use, including generating a detailed timeline of consumption. In vitro exposure of HepaRG liver cells to EtOH resulted in the generation of ethylated phosphorylcholine (EtOChoP). This is the first study to investigate the in vivo presence of EtOChoP and its occurrence in medico-legal samples. Proof-of-concept and observational studies assessed EtOChoP, PEth, EtG, EtS, and EtOH in whole blood, and, when available, other matrices were analyzed for EtG, EtS (plasma, serum, urine, hair), EtOH (urine), and EtOChoP (plasma, serum). A single alcohol exposure event (0.5 g/kg EtOH, with blood EtOH concentration peaking at 0.76 g/L at 100 min) led to EtOChoP presence, and, similar to short-term biomarkers (e.g., EtOH, EtG, and EtS in whole blood), EtOChoP was not detected in the following day(s). However, in the observational study, EtOChoP remained detectable even when short-term biomarkers were absent, resembling long-term biomarkers (PEth and hair EtG). Notably, 14% of samples were positive only for EtOChoP, highlighting the need for additional biomarkers. These findings identify EtOChoP as a promising alcohol (ab)use biomarker formed after EtOH consumption and possibly accumulating during chronic drinking. EtOChoP could potentially differentiate between recent drinking and chronic problematic drinking in individuals with high PEth levels.
饮酒在全球范围内广泛存在，是导致受伤、发病和死亡的主要原因。在临床和法医环境中，使用可靠的生物标志物准确检测酒精使用情况至关重要。直接酒精生物标志物，即乙醇（EtOH）、乙基葡萄糖醛酸苷（EtG）、硫酸乙酯（EtS）、磷脂酰乙醇16:0/18:1（PEth）反映短期和长期饮酒情况。然而，需要具有更高特异性和敏感性的补充生物标志物来更好地评估酒精使用情况，包括生成详细的饮酒时间线。将HepaRG肝细胞体外暴露于EtOH导致产生乙基化磷酸胆碱（EtOChoP）。这是第一项研究EtOChoP在体内的存在情况及其在法医样本中的出现情况的研究。概念验证和观察性研究评估了全血中的EtOChoP、PEth、EtG、EtS和EtOH，并且在可行时，还分析了其他基质中的EtG、EtS（血浆、血清、尿液、毛发）、EtOH（尿液）和EtOChoP（血浆、血清）。单次酒精暴露事件（0.5 g/kg EtOH，血液EtOH浓度在100分钟时峰值达到0.76 g/L）导致EtOChoP出现，并且与短期生物标志物（例如全血中的EtOH、EtG和EtS）类似，在随后的几天中未检测到EtOChoP。然而，在观察性研究中，即使短期生物标志物不存在，EtOChoP仍然可检测到，类似于长期生物标志物（PEth和毛发EtG）。值得注意的是，14%的样本仅EtOChoP呈阳性，突出了对额外生物标志物的需求。这些发现确定EtOChoP是一种有前景的酒精（滥用）生物标志物，在摄入EtOH后形成，并且可能在长期饮酒过程中积累。EtOChoP可能能够区分PEth水平高的个体近期饮酒和长期问题饮酒情况。
