Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
Arch Toxicol. 2024 Jan;98(1):135-149. doi: 10.1007/s00204-023-03631-z. Epub 2023 Dec 5.
Sudden death could occur after assumption of illicit drugs for recreational purposes in adults or after intoxication in children, and toxicological testing would help identify the cause of the death. Analytical methods sensitive and specific for the quantification of a great number of drugs and metabolites in at least 2 matrices should be used. Bile, collected postmortem, may be considered a specimen alternative to blood and urine to perform toxicological testing because of its extended detection window. The present study proposed a LC-MS/MS method to quantify 108 drugs and metabolites in bile. Compounds belonging to the drugs of abuse classes of amphetamines, benzodiazepines, cocaine derivatives, barbiturates, opioids, z-drugs, and psychedelics were analyzed. The sample preparation is simple and does not require solid-phase extraction. The proposed method showed an appropriate selectivity, specificity, accuracy, and precision of the calibrators and quality controls tested (precision < 15%; accuracy < 100 ± 15%). The sensitivity allowed to identify low amounts of drugs (e.g., morphine limit of detection = 0.2 µg/L; limit of quantification = 1.1 µg/L). There is no significant matrix effect, except for buprenorphine and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol. Carry-over was not present. Analytes were stable at least for 1 month at - 20 °C. Analyzing 13 postmortem specimens, methadone (50%), and cocaine (37.5%) resulted to be the most prevalent consumed substances; the concentrations quantified in bile resulted to be higher than the ones in blood suggesting bile as a potential new matrix for identifying illicit drugs and their metabolites.
在成年人出于娱乐目的而使用非法药物或儿童中毒后，可能会发生猝死，毒理学检测将有助于确定死亡原因。应使用至少两种基质中定量检测大量药物和代谢物的灵敏且特异的分析方法。死后采集的胆汁可作为替代血液和尿液进行毒理学检测的标本，因为其检测窗口期更长。本研究提出了一种 LC-MS/MS 方法，用于定量检测胆汁中的 108 种药物和代谢物。分析了属于苯丙胺类、苯二氮䓬类、可卡因衍生物、巴比妥类、阿片类、Z 类药物和迷幻剂等药物滥用类别的化合物。样品制备简单，不需要固相萃取。所提出的方法显示出适当的选择性、特异性、准确性和精密度（精密度 < 15%；准确度 < 100 ± 15%）。该方法的灵敏度足以识别低浓度的药物（例如，吗啡检测限 = 0.2 µg/L；定量限 = 1.1 µg/L）。除了丁丙诺啡和 11-Nor-9-羧基-Δ9-四氢大麻酚外，不存在显著的基质效应。无拖尾现象。分析物在 -20°C 下至少稳定 1 个月。分析了 13 份死后标本，结果表明美沙酮（50%）和可卡因（37.5%）是最常见的消耗物质；胆汁中定量的浓度高于血液中的浓度，提示胆汁可能是一种识别非法药物及其代谢物的潜在新基质。
