Detection and Characterization of the Effect of AB‐FUBINACA and Its Metabolites in a Rat Model

Abstract

Synthetic cannabinoids were originally developed by academic and pharmaceutical laboratories with the hope of providing therapeutic relief from the pain of inflammatory and degenerative diseases. However, recreational drug enthusiasts have flushed the market with new strains of these potent drugs that evade detection yet endanger public health and safety. Although many of these drug derivatives were published in the medical literature, others were merely patented without further characterization. AB‐FUBINACA is an example of one of the new indazole‐carboxamide synthetic cannabinoids introduced in the past year. Even though AB‐FUBINACA has become increasingly prominent in forensic drug and toxicology specimens analyses, little is known about the pharmacology of this substance. To study its metabolic fate, we utilized Wistar rats to study the oxidative products of AB‐FUBINACA in urine and its effect on gene expressions in liver and heart. Rats were injected with 5 mg/kg of AB‐FUBINACA each day for 5 days. Urine samples were collected every day at the same time. On day 5 after treatment, we collected the organs such as liver and heart. The urine samples were analyzed by mass spectrometry, which revealed several putative metabolites and positioning of the hydroxyl addition on the molecule. We used quantitative PCR gene expression array to analyze the hepatotoxicity and cardiotoxicity on these rats and confirmed by real‐time quantitative RT‐PCR. We identified three genes significantly associated with dysfunction of oxidation and inflammation. Our study reports in vivo metabolites of AB‐FUBINACA in urine and its effect on the gene expressions in liver and heart. J. Cell. Biochem. 117: 1033–1043, 2016. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals. Inc.

Analysis of AMB-FUBINACA Biotransformation Pathways in Human Liver Microsome and Zebrafish Systems by Liquid Chromatography-High Resolution Mass Spectrometry

“…As the most abundant metabolites, ester hydrolysis metabolites M3 group plays a very important role in the identification of this drug. However, these metabolites can be formed from other synthetic cannabinoids as well-including AB-FUBINACA (Hsin-Hung Chen et al, 2016). Therefore, identification of these metabolites on their own is not sufficient to indicate AMB-FUBINACA intake.…”

Pharmaco‐toxicological effects of the novel third‐generation fluorinate synthetic cannabinoids, 5F‐ADBINACA, AB‐FUBINACA, and STS‐135 in mice. In vitro and in vivo studies

“…The metabolism of AB‐FUBINACA and STS‐135 has been identified using a hepatocyte model, human liver microsomal incubation, and from human and rat urine samples (Castaneto et al ., ; Ford & Berg, ; Gandhi et al ., ; Hsin‐Hung Chen et al ., ; Sobolevsky, Prasolov, & Rodchenkov, ; Vikingsson et al ., ). For both SCBs, several metabolites of phases I and II have been highlighted.…”

The 2-alkyl-2H-indazole regioisomers of synthetic cannabinoids AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA are possible manufacturing impurities with cannabimimetic activities

“…Forensic chemists and toxicologists have developed methods for the detection of AB-CHMINACA [ 39 , 40 ], AB-FUBINACA [ 41 – 44 ], AB-PINACA [ 41 , 45 , 46 ], 5F-AB-PINACA [ 45 , 46 ], and their metabolites in various biological matrices [ 47 ]. However, the changing legality of these substances, and the development of methods for their detection, increases the likelihood that newer analogues of this class will begin to appear on the drug market.…”