CAMAG DBS Laboratory, CAMAG, Muttenz, Switzerland.
Institute of Forensic Medicine Bern, University of Bern, Bern, Switzerland.
Nat Protoc. 2021 Jan;16(1):283-308. doi: 10.1038/s41596-020-00416-x. Epub 2020 Dec 7.
Phosphatidylethanol (PEth), which is formed by enzymatic reaction between ethanol and phosphatidylcholine, is a direct marker for alcohol usage. PEth has a long elimination half-life (~5-10 d) and specimens can be sampled using minimally invasive microsampling strategies. In combination with rapid analysis procedures PEth has proved to be advantageous for the detection of abstinence over other direct (e.g., ethyl glucuronide in blood, urine or hair) and indirect (e.g., carbohydrate-deficient transferrin in serum) alcohol markers. Although PEth determination is widely applied around the world, laboratory protocols are not standardized. Here we provide general guidelines for the analysis of PEth in dried blood spots (DBSs), including reference material evaluation, synthesis of a deuterated internal standard, preparation of calibration samples (reference material in teetotaller blood), and analyte separation and detection. The protocol contains information to extract the DBSs either manually or with a fully automated autosampler. Extraction of the analytes from DBS filter paper cards is performed using an organic extraction, followed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). For accurate and reliable measurement of PEth, the two most abundant analogs, PEth 16:0/18:1 and PEth 16:0/18:2, are quantified. We show data that provide guidelines on how to interpret the results for both demographic studies and forensic applications. The described protocol can be applied by experienced laboratory staff with basic LC-MS/MS knowledge and takes 2 d to perform.
磷脂酰乙醇(PEth)是由乙醇和磷脂酰胆碱之间的酶促反应形成的,是酒精使用的直接标志物。PEth 的消除半衰期较长(~5-10 天),可以使用微创微采样策略采集样本。与快速分析程序相结合,PEth 已被证明在检测戒断方面优于其他直接(例如血液、尿液或头发中的乙基葡萄糖醛酸)和间接(例如血清中碳水化合物缺乏转铁蛋白)的酒精标志物。尽管 PEth 测定已在全球范围内广泛应用,但实验室方案尚未标准化。在这里,我们提供了分析干血斑(DBS)中 PEth 的一般指南,包括参考物质评估、氘代内标合成、校准样品(戒酒者血液中的参考物质)制备以及分析物分离和检测。该方案包含有关使用手动或全自动自动进样器提取 DBS 的信息。使用有机溶剂萃取从 DBS 滤纸卡中提取分析物,然后进行液相色谱-串联质谱(LC-MS/MS)分析。为了准确可靠地测量 PEth,需要对两种最丰富的类似物,PEth 16:0/18:1 和 PEth 16:0/18:2 进行定量。我们展示的数据提供了如何为人口研究和法医应用解释结果的指南。该描述的方案可以由具有基本 LC-MS/MS 知识的经验丰富的实验室人员应用,并且需要 2 天的时间来执行。