In-depth comparison of the metabolic and pharmacokinetic behaviour of the structurally related synthetic cannabinoids AMB-FUBINACA and AMB-CHMICA in rats (original) (raw)
References (51)
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2021: Trends and Developments (EMCDDA, 2021).
Krotulski, A. J., Mohr, A. L. A., Diamond, F. X. & Logan, B. K. Detection and characterization of the new synthetic cannabinoid APP-BINACA in forensic casework. Drug Test. Anal. 12, 136-144 (2020).
Halter, S. et al. Cumyl-CBMICA: A new synthetic cannabinoid receptor agonist containing a cyclobutyl methyl side chain. Drug Test. Anal. 13, 208-216 (2021).
Tsochatzis, E. D. et al. Identification and analytical characterization of a novel synthetic cannabinoid-type substance in herbal material in Europe. Molecules 26, 793 (2021).
Cannaert, A., Storme, J., Franz, F., Auwärter, V. & Stove, C. P. Detection and activity profiling of synthetic cannabinoids and their metabolites with a newly developed bioassay. Anal. Chem. 88, 11476-11485 (2016).
Antonides, L. H. et al. Shape matters: The application of activity-based in vitro bioassays and chiral profiling to the pharmacological evaluation of synthetic cannabinoid receptor agonists in drug-infused papers seized in prisons. Drug Test. Anal. 13, 628-643 (2021).
Cannaert, A. et al. Synthesis and in vitro cannabinoid receptor 1 activity of recently detected synthetic cannabinoids 4F-MDMB-BICA, 5F-MPP-PICA, MMB-4en-PICA, CUMYL-CBMICA, ADB-BINACA, APP-BINACA,
Fig. 5 Proposed fragmentation for the two SCRAs. Proposed chemical structure for the accurate-mass fragments observed for a AMB-FUBINACA and b AMB-CHMICA. Below the proposed structure of each fragment ion it is displayed its corresponding m/z. 4F-MDMB-BINACA, MDMB-4en-PINACA, A-CHMINACA, 5F-AB- P7AICA, 5F-MDMB-P7AICA, an. ACS Chem. Neurosci. 11, 4434-4446 (2020).
Krotulski, A. J., Cannaert, A., Stove, C. & Logan, B. K. The next generation of synthetic cannabinoids: Detection, activity, and potential toxicity of pent-4en and but-3en analogues including MDMB-4en-PINACA. Drug Test. Anal. 13, 427-438 (2021).
Lie, W. et al. Diagnosing intake and rationalizing toxicities associated with 5F- MDMB-PINACA and 4F-MDMB-BINACA abuse. Arch. Toxicol. 95, 489-508 (2021).
Markin, P. A. et al. Short-and long-term exposures of the synthetic cannabinoid 5F-APINAC induce metabolomic alterations associated with neurotransmitter systems and embryotoxicity confirmed by teratogenicity in zebrafish. Comp. Biochem. Physiol. Part C Toxicol. Pharm. 243, 109000 (2021).
Silva, J. P., Araújo, A. M., de Pinho, P. G., Carmo, H. & Carvalho, F. Synthetic cannabinoids JWH-122 and THJ-2201 disrupt endocannabinoid-regulated mitochondrial function and activate apoptotic pathways as a primary mechanism of in vitro nephrotoxicity at in vivo relevant concentrations. Toxicol. Sci. 169, 422-435 (2019).
Krotulski, A. J., Bishop-Freeman, S. C., Mohr, A. L. A. & Logan, B. K. Evaluation of synthetic cannabinoid metabolites in human blood in the absence of parent compounds: A stability assessment. J. Anal. Toxicol. 45, 60-68 (2021).
Fabregat-Safont, D. et al. Investigation on the consumption of synthetic cannabinoids among teenagers by the analysis of herbal blends and urine samples. J. Pharm. Biomed. Anal. 186, 113298 (2020).
Leong, H. S. et al. Monitoring metabolism of synthetic cannabinoid 4F- MDMB-BINACA via high-resolution mass spectrometry assessed in cultured hepatoma cell line, fungus, liver microsomes and confirmed using urine samples. Forensic Toxicol. 39, 198-212 (2021).
Walle, N. et al. Comparison of in vitro and in vivo models for the elucidation of metabolic patterns of 7-azaindole-derived synthetic cannabinoids exemplified using cumyl-5F-P7AICA. Drug Test. Anal. 13, 74-90 (2021).
Jang, M., Shin, I., Kim, J. & Yang, W. Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry. Forensic Toxicol. 33, 221-234 (2015).
Kadomura, N. et al. In vitro metabolic profiles of adamantyl positional isomers of synthetic cannabinoids. Forensic Toxicol. 39, 26-44 (2021).
Haschimi, B. et al. The novel psychoactive substance Cumyl-CH- MEGACLONE: Human phase-I metabolism, basic pharmacological characterization, and comparison to other synthetic cannabinoid receptor agonists with a γ-carboline-1-one core. J. Anal. Toxicol. 45, 277-290 (2021).
Fabregat-Safont, D. et al. Comprehensive investigation on synthetic cannabinoids: Metabolic behavior and potency testing, using 5F-APP-PICA and AMB-FUBINACA as model compounds. Drug Test. Anal. 11, 1358-1368 (2019).
Mardal, M., Annaert, P., Noble, C., Oorts, M. & Linnet, K. Metabolism of the synthetic cannabinoid 5F-PY-PICA by human and rat hepatocytes and identification of biliary analytical targets by directional efflux in sandwich- cultured rat hepatocytes using UHPLC-HR-MS/MS. J. Pharm. Biomed. Anal. 149, 296-307 (2018).
Savchuk, S. et al. In vivo metabolism of the new synthetic cannabinoid APINAC in rats by GC-MS and LC-QTOF-MS. Forensic Toxicol. 35, 359-368 (2017).
Jang, M. et al. Determination of urinary metabolites of XLR-11 by liquid chromatography-quadrupole time-of-flight mass spectrometry. Anal. Bioanal. Chem. 408, 503-516 (2016).
Vikingsson, S., Gréen, H., Brinkhagen, L., Mukhtar, S. & Josefsson, M. Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry. Drug Test. Anal. 8, 950-956 (2016).
Diao, X. & Huestis, M. A. New synthetic cannabinoids metabolism and strategies to best identify optimal marker metabolites. Front. Chem. 7, 1-15 (2019).
Liu, F. et al. A comparative study on pharmacokinetics and tissue distribution of 5-hydroxy-4-methoxycanthin-6-one and its metabolite in normal and dextran sodium sulfate-induced colitis rats by HPLC-MS/MS. J. Pharm. Pharmacol. 72, 1761-1770 (2020).
Lobato-Freitas, C. et al. Overview of synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, analytical, and forensic implications. Pharmaceuticals 14, 186 (2021).
Mardal, M. et al. Metabolism of the synthetic cannabinoids AMB-CHMICA and 5C-AKB48 in pooled human hepatocytes and rat hepatocytes analyzed by UHPLC-(IMS)-HR-MS E. J. Chromatogr. B 1083, 189-197 (2018).
Fabregat-Safont, D., Sancho, J. V., Hernández, F. & Ibáñez, M. The key role of mass spectrometry in comprehensive research on new psychoactive substances. J. Mass Spectrom. 56, e4673 (2021).
Franz, F., Angerer, V., Moosmann, B. & Auwärter, V. Phase I metabolism of the highly potent synthetic cannabinoid MDMB-CHMICA and detection in human urine samples. Drug Test. Anal. 9, 744-753 (2017).
Carlier, J., Diao, X., Wohlfarth, A., Scheidweiler, K. & Huestis, M. A. In vitro metabolite profiling of ADB-FUBINACA, a new synthetic cannabinoid. Curr. Neuropharmacol. 15, 682-691 (2017).
Sauerschnig, C., Doppler, M., Bueschl, C. & Schuhmacher, R. Methanol generates numerous artifacts during sample extraction and storage of extracts in metabolomics research. Metabolites 8, 1 (2017).
Riedmaier, S. et al. Paraoxonase (PON1 and PON3) polymorphisms: Impact on liver expression and atorvastatin-lactone hydrolysis. Front. Pharmacol. 2, 1-20 (2011).
Carlier, J., Diao, X., Sempio, C. & Huestis, M. A. Identification of new synthetic cannabinoid ADB-CHMINACA (MAB-CHMINACA) metabolites in human hepatocytes. AAPS J. 19, 568-577 (2017).
Wong, S. H., Bell, S. G., & De Voss, J. J. P450 catalysed dehydrogenation. Pure Appl. Chem. 89, 841-852 (2017).
Martignoni, M., Groothuis, G. M. M. & de Kanter, R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition, and induction. Expert Opin. Drug Metab. Toxicol. 2, 875-894 (2006).
Miners, J. O., Coulter, S., Tukey, R. H., Veronese, M. E. & Birkett, D. J. Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R-and S-naproxen. Biochem. Pharmacol. 51, 1003-1008 (1996).
Obach, R. S., Pablo, J. & Mash, D. C. Cytochrome P4502D6 catalyzes the O-demethylation of the psychoactive alkaloid ibogaine to 12-hydroxyibogamine. Drug Metab. Dispos. 26, 764-768 (1998).
Cannaert, A., Franz, F., Auwärter, V. & Stove, C. P. Activity-based detection of consumption of synthetic cannabinoids in authentic urine samples using a stable cannabinoid reporter system. Anal. Chem. 89, 9527-9536 (2017).
Freitas, H. R. et al. Polyunsaturated fatty acids and endocannabinoids in health and disease. Nutr. Neurosci. 21, 695-714 (2018).
Fabregat-Safont, D. et al. Understanding the pharmacokinetics of synthetic cathinones: Evaluation of the blood-brain barrier permeability of 13 related compounds in rats. Addict. Biol. 26, e12979 (2021).
Presley, B. C., Castaneto, M. S., Logan, B. K. & Jansen-Varnum, S. A. Assessment of synthetic cannabinoid FUB-AMB and its ester hydrolysis metabolite in human liver microsomes and human blood samples using UHPLC-MS/MS. Biomed. Chromatogr. 34, 1-10 (2020).
Castaneto, M. S. et al. Identification of AB-FUBINACA metabolites in human hepatocytes and urine using high-resolution mass spectrometry. Forensic Toxicol. 33, 295-310 (2015).
Franz, F., Haschimi, B., King, L. A. & Auwärter, V. Extraordinary long detection window of a synthetic cannabinoid metabolite in human urine-Potential impact on therapeutic decisions. Drug Test. Anal. 12, 391-396 (2020).
Adams, A. J. et al. "Zombie" outbreak caused by the synthetic cannabinoid AMB-FUBINACA in New York. N. Engl. J. Med. 376, 235-242 (2017).
Fabregat-Safont, D. et al. Identification and characterization of a putative new psychoactive substance, 2-(2-(4-chlorophenyl)acetamido)-3- methylbutanamide, in Spain. Drug Test. Anal. 9, 1073-1080 (2017).
Fabregat-Safont, D. et al. Reporting the novel synthetic cathinone 5-PPDI through its analytical characterization by mass spectrometry and nuclear magnetic resonance. Forensic Toxicol. 36, 447-457 (2018).
Carlier, J. et al. Pharmacodynamic effects, pharmacokinetics, and metabolism of the synthetic cannabinoid AM-2201 in male rats. J. Pharmacol. Exp. Ther. 367, 543-550 (2018).
Fabregat-Safont, D. et al. Metabolic profiling of four synthetic stimulants, including the novel indanyl-cathinone 5-PPDi, after human hepatocyte incubation. J. Pharm. Anal. 10, 147-156 (2020).
Fabregat-Safont, D. et al. Proposal of 5-methoxy-N-methyl-N- isopropyltryptamine consumption biomarkers through identification of in vivo metabolites from mice. J. Chromatogr. A 1508, 95-105 (2017).
Ibáñez, M. et al. Analytical strategy to investigate 3,4-methylenedioxypyrovalerone (MDPV) metabolites in consumers' urine by high-resolution mass spectrometry. Anal. Bioanal. Chem. 408, 151-164 (2016). acknowledge financial support from Ministerio de Economía y Competitividad-FEDER (BFU2016-77691-C2-1-P) and the Generalitat Valenciana (PROMETEO/2016/076).