Fatal intoxication involving 2,5-dimethoxy-4-chloroamphetamine (DOC): A case report

Abstract

2,5-dimethoxy-4-chloroamphetamine (DOC) is a substituted alpha-methylated phenethylamine, which was identified for the 1st time in 2009 in France, but is not classified as an illegal narcotic. This report presents a fatal intoxication involving consumption of DOC with analysis of multiple matrices. A 26-year-old man was found dead in his friend's apartment after a party. At place, numerous bottles of alcohol were discovered. The man was known as a cannabis smoker. Except the observation of a multi-visceral congestion and oedematous lungs, no obvious cause of death was identified at autopsy. Peripheral blood (PB), cardiac blood (CB), urine and bile were collected. Immunological screening for amphetamine, methamphetamine, opiates, cannabinoids, cocaine, buprenorphine, methadone and MDMA was performed on urine. Quantification of cannabinoids was performed on PB by GC-MS/MS. Analysis of ethanol and other volatile compounds was performed on PB and urine using HS-GC-MS. Ethylglucuronide (EtG) was quantified in PB and urine by GC-MS/MS. General unknown screening (GUS) was performed on PB by GC-MS and LC-PDA/MS. DOC was quantified in bloods, urine and bile by UHPLC-MS/MS after liquid-liquid extraction, using MBDB-d5 as internal standard. The assay was validated on whole blood for linearity (range: 2.0 to 500 ng/mL), selectivity, precision and accuracy at limit of quantification (LOQ: 2.0 ng/mL) and at high-level concentration (High QC: 400 ng/mL). The dilution process was validated in urine (dilution factor 1/10). Immunological screening was positive for cannabinoids. Confirmation in PB quantified THC, 11-OH-THC and THC-COOH at 3.40, 2.10 and 36.0 ng/mL, respectively. Ethanol analyses were negative but EtG was quantified at 0.48 μg/mL and 161 μg/mL in PB and urine, respectively. Mirtazapine was quantified at therapeutic concentration (20 ng/mL) in PB. DOC was detected on GUS by GC-MS and LC-PDA/MS. The method of DOC quantification was validated by measurement of accuracy and precision at the LOQ (104% and 12.6%) and at the High QC (97.4% and 8.5%). The 10-fold dilution process in urine was validated in term of accuracy (100%) and precision (4.1%). Selectivity was validated by analyzing 6 blank samples and no interference was observed at DOC retention time. In the present case, DOC was quantified at 104 ng/mL, 322 ng/mL, 648 ng/mL and 371 ng/mL in PB, CB, urine and bile respectively. Presence of cannabinoids and EtG in blood and urine suggest alcohol and cannabis consumption several hours preceding the death. Reports of use of DOC have mainly described non-fatal intoxications, with reported blood concentrations from < 10 to 18 ng/mL (Abbara. TOXAC 2017;29:82–89). At our best knowledge, only one fatal case has been reported in the literature (Barnett. JAT 2014;38:589–591), in which DOC blood and urine concentrations were 377 and 3193 ng/mL. Difference between PB and CB concentrations in the present case could be explain by postmortem redistribution. In the present case, the circumstances of death, autopsy findings and toxicological results were consistent with a toxic cause of death by DOC overdose in association with cannabis consumption.