BACKGROUND: The potent synthetic cannabinoid ADB-BUTINACA (also known as ADB-BINACA) was implicated in three fatal intoxications. Post-mortem samples, including femoral and heart blood, urine, gastric content, bile, vitreous humor, cerebrospinal fluid, and various tissues (brain, kidney, liver, lung, muscle), were analyzed. All cases were mixed intoxications with pregabalin, heroin, ketamine, MDPHP, or ethanol.

METHODS: Post-mortem examinations were performed in all three fatalities. Blood and urine were screened by immunoassay, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for drugs. ADB-BUTINACA was quantified by standard addition in all matrices except vitreous humor and cerebrospinal fluid. For assessing the contribution of ADB-BUTINACA, a Toxicological Significance Score (TSS) was assigned to each case. Metabolite profiles received from analysis of post-mortem matrices were compared with HepG2 cell and human liver microsome data. Additionally, compound stability was assessed over 12 weeks in whole blood.

RESULTS: Femoral blood concentrations of ADB-BUTINACA ranged from 4.2-8.2 ng/mL, and in heart blood from 5.7-11 ng/mL. Brain tissue contained 1.0-6.2 ng/g, and vitreous humor 0.33-2.1 ng/mL. TSS for ADB-BUTINACA of 1 - 3 were assigned for all cases. Heart-to-femoral blood ratios (1.3-1.8) indicated relatively low post-mortem redistribution. Metabolite profile assessment indicated that detection of metabolic biomarkers such as the dihydrodiol could be relevant in urine and bile. Matrix storage at -20 °C is highly recommended to avoid stability issues.

CONCLUSION: ADB-BUTINACA was detected in all investigated matrices, with the highest concentrations observed in liver, lung, and kidney tissue. The elevated levels in these organs likely reflect their lipophilicity as well as their involvement in absorption (lungs) and metabolism/excretion processes (liver and kidneys). The results of this study may enhance interpretation of toxicological findings in similar cases.