Metabolism of 4F‐MDMB‐BICA in zebrafish by liquid chromatography–high resolution mass spectrometry

Abstract

In this study, in vivo metabolic studies of the synthetic cannabinoid 4F-MDMB-BICA were investigated using zebrafish models. The metabolites were identified and structurally illustrated by liquid chromatography-high resolution mass spectrometry.Fourteen phase-I metabolites and four phase-II metabolites were generated from zebrafish. The main metabolic pathways of the phase-I metabolism included N-dealkylation, N-dealkylation combined with hydroxylation, amide hydrolysis, oxidative defluorination, oxidative defluorination to butyric acid, acetic acid formation at the indole side chain, hydroxylation, ester hydrolysis followed by hydroxylation, dehydrogenation, dehydrogenation, and N-dealkylation, and oxidative defluorination subsequently combined with dehydrogenation. The main biotransformations of the phase-II metabolism were glucuronidation and sulfation. Two phase-I metabolites (A1 and A11) and four phase-II metabolites (A2, A3, A4, and A12) were reported for the first time. A14, which was confirmed in human biological samples, was detected only in zebrafish samples but not found in human liver microsome incubation study.The current study indicates that the zebrafish model is a promising tool for elucidating the metabolism of NPS in the future.

Metabolism of ADB‐FUBIATA in zebrafish and pooled human liver microsomes investigated by liquid chromatography–high‐resolution mass spectrometry

“…11 Researchers have studied the metabolism of 4F-MDMB-BICA, AMB-FUBINACA, and MDMB-CHMINACA in the zebrafish model, which provides a more authentic characterization of metabolites. 13,37,40 Zebrafish resemble mammals in their physiology, morphology, and histology, and they show 70% genetic homology with humans. [41][42][43][44] The small size, easy maintenance, low cost, and high reproductive rate are considerable advantages for whole-organism studies with ethical permission in biology, toxicology, drug discovery, and neurobiology.…”

“…However, the lack of other enzymes, such as aldehyde oxidase, N ‐acetyltransferase, glutathione S ‐transferase, and sulfotransferase, 39 creates major metabolite discrepancies, particularly of 5F‐AKB‐48 and AM‐2201, between pHLMs and human urine following SC intake 11 . Researchers have studied the metabolism of 4F‐MDMB‐BICA, AMB‐FUBINACA, and MDMB‐CHMINACA in the zebrafish model, which provides a more authentic characterization of metabolites 13,37,40 . Zebrafish resemble mammals in their physiology, morphology, and histology, and they show 70% genetic homology with humans 41–44 .…”

Analysis of indole and indazole amides synthetic cannabinoids by differential Raman spectroscopy based on ANN

“…Abusive use of such drugs could cause rapid heart rate, time illusion, nausea, vomiting, difficulty in concentrating, and neuron destruction leading to delusional symptoms, etc. [1][2][3][4]. With the rapid development of related technologies, the smoking carriers of such drugs were more diverse, more types, and more and more similar in appearance and form to legal products, which made the supervision of such drugs more difficult.…”