Document Type
Article
Publication Date
7-29-2022
Abstract
Tryptamine intoxications and fatalities are increasing, although these novel psychoactive substances (NPS) are not controlled in most countries. There are few data on the metabolic pathways and enzymes involved in tryptamine biotransformation. 4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DiPT) is a synthetic tryptamine related to 4-hydroxy-N,N-diisopropyltryptamine (4-OH-DiPT), 4-acetyloxy-N,N-dipropyltryptamine (4-AcO-DPT), and 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT). The aim of this study was to determine the best 4-AcO-DiPT metabolites to identify 4-AcO-DiPT consumption through human hepatocyte metabolism and high-resolution mass spectrometry. 4-AcO-DiPT metabolites were predicted in silico with GLORYx freeware to assist in metabolite identification. 4-AcO-DiPT was incubated with 10-donor-pooled human hepatocytes and sample analysis was performed with reversed-phase liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS/MS) in positive- and negative-ion modes. Software-assisted LC-HRMS/MS raw data mining was performed. A total of 47 phase I and II metabolites were predicted, and six metabolites were identified after 3 h incubation following ester hydrolysis, O-glucuronidation, O-sulfation, N-oxidation, and N-dealkylation. All second-generation metabolites were derived from the only first-generation metabolite detected after ester hydrolysis (4-OH-DiPT). The metabolite with the second-most-intense signal was 4-OH-iPT-sulfate followed by 4-OH-DiPT-glucuronide, indicating that glucuronidation and sulfation are common in this tryptamine’s metabolic pathway. 4-OH-DiPT, 4-OH-iPT, and 4-OH-DiPT-N-oxide are suggested as optimal biomarkers to identify 4-AcO-DiPT consumption.
Recommended Citation
Malaca, Sara; Huestis, Marilyn A; Lattanzio, Leonardo; Marsella, Luigi T; Tagliabracci, Adriano; Carlier, Jeremy; and Busardò, Francesco P, "Human Hepatocyte 4-Acetoxy- N, N-Diisopropyltryptamine Metabolite Profiling by Reversed-Phase Liquid Chromatography Coupled with High-Resolution Tandem Mass Spectrometry" (2022). College of Health Professions Faculty Papers. Paper 7.
https://jdc.jefferson.edu/jchpfp/7
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Language
English
Comments
This article is the author's final published version in Metabolites, Volume 12, Issue 8, August 2022, Article number 705.
the published version is available at https://doi.org/10.3390/metabo12080705.
Copyright © 2022 by the authors
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).