Toxicological Investigations in a Death Involving 2,5-Dimethoxy-4-Chloamphetamine (DOC) Performed on an Exhumed Body

Abstract

Abstract 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.