Retrospective identification of 25I-NBOMe metabolites in an intoxication case

SummaryNew psychoactive substances (NPS) recently appeared on the recreational drugs market. Among them, N-Benzyl-Oxy-Methyl (NBOMe) derivatives are concern by mainly several reports in the literature of use and associated acute toxicity over the last 6 years, and the majority of the cases are related to 25I-NBOMe. We report a case of severe intoxication with a liquid mixture of NBOMes consumed nasally that has been retrospectively documented by 25I-NBOMe and metabolites determinations. A 29-year-old man experienced acute unconsciousness within one hour after a drop instillation in the nose of pink liquid. Initial examination on admission evidenced hypertonia and tremors, then partial seizure with secondary generalization, bilateral and reactive mydriasis, tachycardia, hypertension, hyperthermia and profuse sweating, suggestive of serotonin syndrome. He presented persistent cognitive and psychiatric abnormalities at M8. Liquid chromatography with high-resolution mass detection (LC-HRMS) revealed presence of (i) three NBOMes in the pink liquid with 25I-NBOMe as main component, (ii) 25I-NBOMe in serum sampled at H3 (0.9 μg/L determined using Liquid chromatography with tandem mass spectrometry [LC-MS/MS]) but not in serum sampled at H15, and (iii) seven 25I-NBOMe metabolites in 2 urine samples (H3 and H15): two desmethyl-25I-NBOMes, a desmethyl-hydroxy-25I-NBOMe, a hydroxy-25I-NBOMe, a di-desmethyl-25I-NBome, a desmethyl-25I-NBOMe glucuronide and a hydroxy-25I-NBOMe glucuronide. These metabolites were retrospectively identified following in vitro investigations of NPS metabolism using analysis of samples collected after 25I-NBOMe incubation with a pool of human liver microsomes (HLMs) and cross-checking to in silico predicted biotransformations of the acquired data. The final goal of this analytical strategy is to record all the identified metabolites MS spectra in our HRMS and MS-MS libraries in order to performed routinely efficient detection of NPS users.