Deadly mono-intoxication after ingestion of 4F-MDMB-BICA

Abstract

The synthetic cannabinoid (SC) 4F-MDMB-BICA was detected in the recent past in connection with numerous poisonings and fatalities. SC with a methyl-3,3-dimethylbutanoate structure are often afflicted with a high instability and usually rapidly degraded to the dimethylbutanoic acid metabolite (DBA), frequently resulting in small amounts of parent compound in samples. Here, we report on a fatality of a 41-year-old man who was found unconscious and declared dead after unsuccessful reanimation. At the scene, a few herbal incenses were found near to the deceased. The autopsy did not reveal any macro morphological cause of death. Among other things, a cerebral and pulmonary edema as well as an incipient pneumonia were found. The seized herbal mixtures were grinded and dispersed in ethanol. Aliquots of the supernatants were tested using GC/MS. Urine, heart blood (HB) and stomach contents were screened using GC/MS following liquid-liquid extraction. Additionally, urine and HB were screened following protein precipitation with acetonitrile using LC-QTOF-MS/MS in SWATH mode (column: Macherey-Nagel (MN) Nucleoshell RP 18 100 × 2 mm, 2.7 μm; MS: SCIEX QTOF 6600+, ESI+). Brain, lung, liver and kidney tissues were homogenized 1 + 4, bile fluid 1 + 9 with water. 4F-MDMB-BICA and DBA were quantified using AB-FUBINACA-D4 as internal standard in tissues as well as bile fluid, HB and peripheral blood (PB) after standard addition, enzymatic cleavage and solid phase extraction using LC-MS/MS (column: MN Nucleodur C18 Gravity 150 × 2 mm, 5 μm; MS: Thermo Fisher TSQ, ESI+). 4F-MDMB-BICA could be detected in every seized herbal mixture, one sample additionally contained ADB-BUTINACA. Besides ibuprofen, 4F-MDMB-BICA and several metabolites were detected in urine, HB and stomach contents. Quantification of the parent substance revealed concentrations of 18 ng/mL in HB, 11 ng/mL in PB, 12 ng/mL in bile fluid as well as low concentrations in other tissues. DBA was detected at concentrations of 100 ng/mL in HB, 31 ng/mL in PB, 96 ng/g in lung, 57 ng/g in kidney, 2 ng/g in brain and 9500 ng/mL in bile fluid. ADB-BUTINACA could not be found in any specimen. The relatively high concentrations of DBA in lung could indicate an acute pulmonary intake closely related to death. The concentrations in HB could have been elevated because of postmortem redistribution. The extremely high concentrations of DBA in bile fluid might be the result of a repeated consumption as well as an enterohepatic circulation. The results of the analyses indicate death due to an acute intoxication of 4F-MDMB-BICA. In contrast to most reported fatalities, the presented case could be attributed to a mono-intoxication after SC consumption.