Title:In Vitro Metabolite Identification Studies for the New Psychoactive Substances Furanylfentanyl, TFMPP, and 5-MeO-DALT in Human Liver
Microsomes
Volume: 18
Issue: 9
Author(s): Tian Zheng*, Liang Wu, Guoping Wu, Yifan Chen and Shuhan Zhou
Affiliation:
- Department of Forensic Science, Jiangsu Police Institute, Nanjing 210031, China
Keywords:
New psychoactive substances, metabolite identification, furanyl fentanyl, TFMPP, 5-MeO-DALT, human liver microsomes.
Abstract:
Aims: Understand the metabolic behavior of new psychoactive substances, furanyl fentanyl,
TFMPP, and 5-MeO-DALT.
Background: New psychoactive substances (NPS) are associated with several health and social harms on
both the individual and societal levels. Many are not regulated and have become increasingly popular
among drug users worldwide. The lack of clinical studies on the effects and toxicity of these drugs has
made the interpretation of their toxicological symptoms difficult.
Objective: Perform an in vitro metabolism study of new psychoactive substances furanyl fentanyl,
TFMPP, and 5-MeO-DALT, revealing their possible metabolites and metabolic pathways in the human
liver microsome.
Methods: A regular human liver microsomal system was used to investigate the potential biotransformation
of furanyl fentanyl, TFMPP, and 5-MeO-DALT in vitro, and high-resolution mass spectrometry
(LC-Q/TOF-MS) was used to perform metabolite detection and identification.
Results: The three components were substantially metabolized in 4 hours with varied metabolic pathways,
and most of the metabolites were generated through phase I metabolic reactions. Furanyl fentanyl
underwent the metabolic pathways of epoxidation and hydration, furanyl ring-opening and oxidation,
hydroxylation, hydrolysis of the amide group, and N-dealkylation; TFMPP underwent the metabolic
pathways of hydroxylation, and the successive piperazidine ring scission; while 5-MeO-DALT underwent
the metabolic pathways of O-demethylation and glucuronidation, dihydroxylation, hydroxylation, oxidation,
O-demethylation, N-dealkylation and methylation and N-dealkylation.
Conclusion: Our data would contribute to a better understanding of furanyl fentanyl, TFMPP, and 5-
MeO-DALT in their in vitro metabolism study, which was beneficial to predicting their metabolic behavior
in vivo, and promoting their drug monitoring in both clinically used and socially/illegally abused.