Metabolic Profile Determination of NBOMe Compounds Using Human Liver Microsomes and Comparison with Findings in Authentic Human Blood and Urine

J Anal Toxicol. 2017 Sep 1;41(7):646-657. doi: 10.1093/jat/bkx029.

Abstract

The emergence of novel psychoactive substances (NPS) such as hallucinogenic NBOMes (N-methoxybenzyl derivatives of 2C phenethylamines) in the past few years into the recreational drug market has introduced various challenges in forensic analytical toxicology in regard to adequate and timely detection of these compounds. This is especially true in samples from individuals who have experienced severe and fatal intoxications. The aim of this research was to identify the major Phase I metabolites of selected NBOMe compounds to generate a predicted human metabolic pathway of these substances. An in vitro incubation method of pooled human liver microsomes (HLMs) with four (4) NBOMes was used to identify major metabolites. These metabolic products were identified and confirmed from accurate mass findings of samples analyzed by Ultra Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry. The most common biotransformations observed among this group of NBOMes include O-demethylations at the three methoxy groups, hydroxylations and reduction at the amine group. Other metabolic products observed include positional isomers from various hydroxylation possibilities on the benzene ring and alkyl chains, and secondary metabolism resulting in multiple combinations of the reactions. Many of the major metabolites were subsequently identified in authentic human samples of blood and urine from drug users.

MeSH terms

  • Designer Drugs / metabolism*
  • Hallucinogens / blood
  • Hallucinogens / metabolism*
  • Hallucinogens / urine
  • Humans
  • Illicit Drugs / blood
  • Illicit Drugs / metabolism*
  • Illicit Drugs / urine
  • Metabolome / physiology
  • Microsomes, Liver / metabolism*
  • Phenethylamines / analysis
  • Phenethylamines / blood
  • Phenethylamines / metabolism*
  • Phenethylamines / urine
  • Substance Abuse Detection / methods

Substances

  • Designer Drugs
  • Hallucinogens
  • Illicit Drugs
  • Phenethylamines