A lethal case of 4F-MDMB-BINACA poisoning

Abstract

Quantify 4F-MDMB-BINACA and its metabolites, 4F-MDMB-BINACA-butanoic acid and 4F-MDMB-BINACA-4-OH, in postmortem blood samples of a synthetic cannabinoid (SC) poisoning case. 1 mL of bloods was mixed with 3 mL of 0.1 M phosphate buffer (pH 6.0). JWH-018-D9 and JWH-018-N-5-OH-D5 (100 μL, 500 pg/mL) was spiked as internal standards. The samples were vortexed vigorously and sonicated for 15 min. After centrifugation at 3500 rpm for 5 min, the supernatant was loaded onto the Bond Elut Certify cartridge (Agilent Technologies) preconditioned with methanol and 0.1 M phosphate buffer (pH 6.0), sequentially. The cartridge was washed with 3 mL of DW and 2 mL of 0.2 M acetic acid sequentially, and eluted with 3 mL of chloroform-acetone (50:50) and 3 mL of ethyl acetate-ammonia (98:2). The eluates were collected in a glass tube, and evaporated to dryness under nitrogen gas at 45 °C. The residues were reconstituted with 150 μL of methanol and filtered (0.22 μm, PVDF). Finally, 5 μL aliquot was injected into LC-MS/MS. The chromatographic separation was performed in a Zorbax Eclipse Plus C18 (RRHD 2.1 × 100 mm, 1.8 μm, Agilent Technologies). The mobile phase was a gradient prepared from 2 mM ammonium formate/0.2% formic acid in water (A) and in methanol (B). The flow rate was 300 μL/min, and the total run time was 12 min. The multiple reaction monitoring (MRM) data were achieved with electrospray ionization in positive ion mode. Two MRM transitions were selected for each analyte. A 29 year-old male Kazakh worker was found unconscious in his bath room by his brother. There was a small amount of herbal powder near the victim. He died soon after sent to a hospital. No noticeable damage except for chest fractures caused by CPR was found during autopsy. 4F-MDMB-BINACA was detected in the herbal powder. 4F-MDMB-BINACA and its metabolites were found in his bloods. The concentrations of 4F-MDMB-BINACA, 4F-MDMB-BINACA-butanoic acid, and 4F-MDMB-BINACA-4-OH in his femoral blood were 0.80 μg/L, 18.36 μg/L, and 0.36 μg/L, and those in his heart blood were 2.05 μg/L, 52.58 μg/L, and 0.46 μg/L, respectively. 4F-MDMB-BINACA was not found in his gastric content. The concentrations of 4F-MDMB-BINACA and its metabolites in the victim's bloods were relatively high according to a previous study (4F-MDMB-BINACA 0.10-2.90 μg/L, 4F-MDMB-BINACA-butanoic acid 0.12–9.05 μg/L, 4F-MDMB-BINACA-4-OH 0.21 μg/L in 6 postmortem bloods, Yeter O, JOTCSA, 2020, 7(3), 827-32). The especially high 4F-MDMB-BINACA-butanoic acid concentration might result from degradation due to the poor stability of a methyl ester functional group of 4F-MDMB-BINACA in blood (Krotulski A, Journal of Analytical Toxicology, 2021, 45, 60-8), which implies that the initial blood concentration of 4F-MDMB-BINACA could have been much higher. 4F-MDMB-BINACA and its metabolites were quantified in the bloods of a fatal SC poisoning case victim for the first time in South Korea. The concentrations of 4F-MDMB-BINACA and 4F-MDMB-BINACA-butanoic acid should be both considered for the interpretation of 4F-MDMB-BINACA fatal toxicity.