Study of the in vitro and in vivo metabolism of the tryptamine 5‐MeO‐MiPT using human liver microsomes and real case samples

The synthetic tryptamine 5-MeO-MiPT, a hallucinogenic drug recently abused in Germany and Switzerland, was identified in a case of intoxication involving a naked, agitated, and aggressive man. Metabolites were characterized in pooled human liver microsomes, blood, and urine using LC–HRMS/MS. Seven phase I metabolites were found in vitro; four in blood and seven in urine. The most abundant metabolites resulted from demethylation and hydroxylation. Blood concentration was 160 ng/mL; urine concentration was 3380 ng/mL. Cocaine, cocaethylene, methylphenidate, and ritalinic acid were also detected in urine. Four metabolites—5-MeO-NiPT, 5-OH-MiPT, 5-MeO-MiPT-N-oxide, and OH-5-MeO-MiPT—are recommended as biomarkers for detecting consumption.

Study at a glance

Abstract

Abstract The synthetic tryptamine 5‐methoxy‐ N ‐methyl‐ N ‐isopropyltryptamine (5‐MeO‐MiPT) has recently been abused as a hallucinogenic drug in Germany and Switzerland. This study presents a case of 5‐MeO‐MiPT intoxication and the structural elucidation of metabolites in pooled human liver microsomes (pHLM), blood, and urine. Microsomal incubation experiments were performed using pHLM to detect and identify in vitro metabolites. In August 2016, the police encountered a naked man, agitated and with aggressive behavior on the street. Blood and urine samples were taken at the hospital and his premises were searched. The obtained blood and urine samples were analyzed for in vivo metabolites of 5‐MeO‐MiPT using liquid chromatography–high resolution tandem mass spectrometry (LC–HRMS/MS). The confiscated pills and powder samples were qualitatively analyzed using Fourier transform infrared (FTIR), gas chromatography–mass spectrometry (GC–MS), LC‐HRMS/MS, and nuclear magnetic resonance (NMR). 5‐MeO‐MiPT was identified in 2 of the seized powder samples. General unknown screening detected cocaine, cocaethylene, methylphenidate, ritalinic acid, and 5‐MeO‐MiPT in urine. Seven different in vitro phase I metabolites of 5‐MeO‐MiPT were identified. In the forensic case samples, 4 phase I metabolites could be identified in blood and 7 in urine. The 5 most abundant metabolites were formed by demethylation and hydroxylation of the parent compound. 5‐MeO‐MiPT concentrations in the blood and urine sample were found to be 160 ng/mL and 3380 ng/mL, respectively. Based on the results of this study we recommend metabolites 5‐methoxy‐ N ‐isopropyltryptamine (5‐MeO‐NiPT), 5‐hydroxy‐ N ‐methyl‐ N ‐isopropyltryptamine (5‐OH‐MiPT), 5‐methoxy‐ N ‐methyl‐ N ‐isopropyltryptamine‐ N ‐oxide (5‐MeO‐MiPT‐ N ‐oxide), and hydroxy‐5‐methoxy‐ N ‐methyl‐ N ‐isopropyltryptamine (OH‐5‐MeO‐MiPT) as biomarkers for the development of new methods for the detection of 5‐MeO‐MiPT consumption, as they have been present in both blood and urine samples.