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Toxicological Investigations in a Death Involving 2,5-Dimethoxy-4-Chloamphetamine (DOC) Performed on an Exhumed Body
Journal of Analytical Toxicology ( IF 2.3 ) Pub Date : 2020-08-29 , DOI: 10.1093/jat/bkaa112
Frédéric Aknouche 1 , Alice Ameline 2 , Angeline Kernalleguen 1 , Nadia Arbouche 2 , Christophe Maruejouls 1 , Pascal Kintz 2, 3
Affiliation  

During a party in another country, several adults sniffed a powder presented as being lysergic acid diethylamide (LSD). The next morning, two subjects, including a French citizen, were found dead. After a body examination that concluded that the death was due to respiratory and cardiac collapses, the French citizen’s corpse was returned to France and buried. Four years later, the body was exhumed, and an autopsy that did not reveal traumatic injury was performed. During the autopsy, biological specimens were collected. A comprehensive toxicological screening, followed by confirmation using ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS-MS) revealed the presence of 2,5-dimethoxy-4-chloamphetamine (DOC) in all specimens: liver (99 ng/g), spleen (28 ng/g), bone (14 ng/g), lung (15 ng/g) and pubic hair (32 pg/mg). No other drug, including pharmaceuticals and drugs of abuse were identified, but the circumstances of specimen collection can influence drug stability. Literature survey about DOC stability in biological material did not contribute in interpretation as there is no data dealing with storage for about 4 years before quantitative analysis. A stability study was performed at the laboratory. Blank blood was spiked with DOC at 1 mg/L, stored at + 4°C and −20°C and regularly tested over 6 months. The percentages of concentration remaining from the initial concentration of DOC stored for 6 months at + 4°C and −20°C were 53% and 59%, respectively. To characterize the metabolite(s) of DOC, the drug was incubated with a pool of human hepatic microsomes and the cofactors required to ensure the functioning of the main phase I enzymes. The incubation media were analyzed by liquid chromatography (LC) coupled to high-resolution mass spectrometry (MS), and the results showed hydroxy-DOC. However, the hydroxy-metabolite was not identified in the liver or spleen of the subject. Although the French pathologist considered that it was more likely than not a toxic death, it is difficult to attribute the death to DOC alone, as it was impossible to test for ethanol and other chemically instable drugs. This case presents original data, which can be useful to increase the knowledge in designer drug toxicity.

中文翻译:

在尸体上进行的涉及2,5-二甲氧基-4-氯苯丙胺(DOC)死亡的毒理学调查

在另一个国家的聚会中,几名成年人闻着一种称为麦角酰二乙胺(LSD)的粉末。第二天早晨,发现包括法国公民在内的两人死亡。经过尸体检查得出死亡原因是呼吸和心脏衰竭之后,法国公民的尸体被送回法国并埋葬。四年后,尸体被挖掘出,并进行了不显示创伤性损伤的尸检。在尸检期间,收集了生物学标本。进行了全面的毒理学筛选,然后使用超高效液相色谱串联质谱(UHPLC-MS-MS)进行了确认,结果表明,所有标本中均存在2,5-二甲氧基-4-氯苯丙胺(DOC):肝脏(99 ng / g ),脾脏(28 ng / g),骨骼(14 ng / g),肺(15 ng / g)和阴毛(32 pg / mg)。没有发现其他药物,包括药物和滥用药物,但标本采集的情况会影响药物的稳定性。有关生物材料中DOC稳定性的文献调查对解释没有帮助,因为在进行定量分析之前约4年没有数据涉及存储。在实验室进行了稳定性研究。用1 mg / L的DOC注入空白血液,储存在+ 4°C和-20°C下,并定期检查6个月。从在+ 4°C和-20°C下存储6个月的DOC初始浓度中剩余的浓度百分比分别为53%和59%。为了表征DOC的代谢产物,将药物与人肝微粒体库和确保主要I期酶功能所需的辅因子一起孵育。通过液相色谱(LC)结合高分辨率质谱(MS)对孵育培养基进行分析,结果显示了羟基DOC。然而,在受试者的肝脏或脾脏中未鉴定出羟基代谢物。尽管法国病理学家认为这很可能是中毒死亡,但很难将死亡归因于DOC,因为无法测试乙醇和其他化学不稳定药物。本案例提供了原始数据,可用于增加设计者药物毒性方面的知识。尽管法国病理学家认为这很可能是中毒死亡,但很难将死亡归因于DOC,因为无法测试乙醇和其他化学不稳定药物。本案例提供了原始数据,可用于增加设计者药物毒性方面的知识。尽管法国病理学家认为这很可能是中毒死亡,但很难将死亡归因于DOC,因为无法测试乙醇和其他化学不稳定药物。本案例提供了原始数据,可用于增加设计者药物毒性方面的知识。
更新日期:2020-08-29
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