α-Methyltryptamine (α-MT) Metabolite Profiling in Human Hepatocyte Incubations and Postmortem Urine and Blood.
Sara MalacaCharline BottinelliLaurent FantonNathalie CartiserFrancesco P BusardòFrancesco Paolo BusardòPublished in: Metabolites (2023)
α-MT is a hallucinogenic and stimulant tryptamine that was involved in several overdose fatalities in the United States and Europe. Analytical toxicology, and particularly the identification of metabolite biomarkers in biological samples, often is the only way to prove tryptamine use in clinical and forensic caseworks. We aimed to identify optimal α-MT metabolite biomarkers of consumption in humans. We identified α-MT metabolites in 10-donor-pooled human hepatocyte incubations and postmortem urine and blood from an α-MT overdose case using in silico metabolite predictions, liquid chromatography high-resolution-tandem mass spectrometry (LC-HRMS/MS), and software-assisted data mining. Nine metabolites were identified in vitro and eight additional metabolites were found in urine; five metabolites were found in blood. Metabolic transformations were hydroxylation, O -sulfation, O -glucuronidation, N -glucuronidation, and N -acetylation, consistent with the metabolism of structural analogues. The findings in hepatocyte incubations and postmortem samples were consistent, proving the in vitro model suitability. We suggest α-MT, hydroxy-α-MT glucuronide, and two hydroxy-α-MT sulfates as biomarkers of α-MT use in non-hydrolyzed urine; we suggest α-MT, two hydroxy-α-MT sulfates and N -acetyl-α-MT as biomarkers of α-MT use in blood. Further studies on α-MT clinical and forensic caseworks with different doses and routes of administration are necessary to better explore α-MT metabolism.
Keyphrases
- liquid chromatography
- tandem mass spectrometry
- high resolution
- ms ms
- mass spectrometry
- endothelial cells
- multiple sclerosis
- ultra high performance liquid chromatography
- machine learning
- high performance liquid chromatography
- high resolution mass spectrometry
- clinical trial
- molecular docking
- liver injury
- big data
- drug induced
- induced pluripotent stem cells
- electronic health record
- phase iii
- artificial intelligence
- molecular dynamics simulations
- pluripotent stem cells