TY - JOUR
T1 - In vitro phase I metabolic profiling of the synthetic cannabinoids AM-694, 5F-NNEI, FUB-APINACA, MFUBINAC and AMB-FUBINACA
AU - Apirakkan, Orapan
AU - Gavrilovic, Ivana
AU - Cowan, David
AU - Abbate, Vincenzo
PY - 2020/7/20
Y1 - 2020/7/20
N2 - Synthetic cannabinoids (SCs) constitute one of the most rapidly expanding class of new psychoactive substances. SCs pose a health threat to the individual and to the public due to their central (psychoactive) and peripheral effects. Their pharmacology and toxicology are poorly understood, and the substances can be unexpectedly toxic and harmful. The metabolism of SCs is also relevant in clinical and forensic toxicology as SCs are excreted in urine mostly as their metabolites. Thus, SC metabolites are widely used as markers for identifying SC intake. Herein, we used human liver microsome systems to study the in vitro phase I metabolic profiling of five SCs, namely AM-694, 5F-NNEI, FUB-APINACA, MFUBINAC, and AMB-FUBINACA. The metabolites were detected and structurally elucidated by liquid chromatography-high resolution mass spectrometry. The main metabolic pathway of AM-694 (benzoyl-indole SC) is oxidative defluorination; 5F-NNEI (naphthyl-indole carboxamide SC) follows amide hydrolysis and monohydroxylation at the naphthyl moiety. However, indazole carboxamide substituted with an adamantyl group, such as FUB-APINACA, is likely to produce (isomeric) hydroxylation of the adamantyl group as the main metabolite species. For the substrates that contain ester bonds in their structure, like MFUBINAC and AMB-FUBINACA, the ester hydrolysis metabolite is predominant.
AB - Synthetic cannabinoids (SCs) constitute one of the most rapidly expanding class of new psychoactive substances. SCs pose a health threat to the individual and to the public due to their central (psychoactive) and peripheral effects. Their pharmacology and toxicology are poorly understood, and the substances can be unexpectedly toxic and harmful. The metabolism of SCs is also relevant in clinical and forensic toxicology as SCs are excreted in urine mostly as their metabolites. Thus, SC metabolites are widely used as markers for identifying SC intake. Herein, we used human liver microsome systems to study the in vitro phase I metabolic profiling of five SCs, namely AM-694, 5F-NNEI, FUB-APINACA, MFUBINAC, and AMB-FUBINACA. The metabolites were detected and structurally elucidated by liquid chromatography-high resolution mass spectrometry. The main metabolic pathway of AM-694 (benzoyl-indole SC) is oxidative defluorination; 5F-NNEI (naphthyl-indole carboxamide SC) follows amide hydrolysis and monohydroxylation at the naphthyl moiety. However, indazole carboxamide substituted with an adamantyl group, such as FUB-APINACA, is likely to produce (isomeric) hydroxylation of the adamantyl group as the main metabolite species. For the substrates that contain ester bonds in their structure, like MFUBINAC and AMB-FUBINACA, the ester hydrolysis metabolite is predominant.
UR - http://www.scopus.com/inward/record.url?scp=85088494266&partnerID=8YFLogxK
U2 - https://doi.org/10.1021/acs.chemrestox.9b00466
DO - https://doi.org/10.1021/acs.chemrestox.9b00466
M3 - Article
SN - 0893-228X
VL - 33
SP - 1653
EP - 1664
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 7
ER -
