High-resolution mass spectrometric determination of the synthetic cannabinoids MAM-2201, AM-2201, AM-2232, and their metabolites in postmortem plasma and urine by LC/Q-TOFMS
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High-resolution mass spectrometry and accurate mass measurement by liquid chromatography/quadrupole-time of flight mass spectrometry (LC/Q-TOFMS) was applied to postmortem plasma and urine specimens from an autopsy of a fatal case involving synthetic cannabinoid use, resulting in the detection of three synthetic cannabinoids: MAM-2201, AM-1220, and AM-2232. We searched for their metabolites existing in postmortem plasma or urine by LC/Q-TOFMS and were able to detect N-dealkylated metabolites, defluorinated and further oxidized metabolites of MAM-2201, and some hydroxylated metabolites. Postmortem plasma concentrations of the parent drugs, N-dealkylated metabolites, and fluorinated and further oxidized metabolites of MAM-2201 were measured, and quantitation results revealed site differences between heart and femoral postmortem plasma concentrations of parent drugs and some metabolites, suggesting postmortem redistribution of the synthetic cannabinoids and their metabolites. Quantitation results suggest that defluorination is a major metabolic pathway for MAM-2201, and N-dealkylation is a common but minor pathway for the naphthoylindole-type synthetic cannabinoids in human.
KeywordsSynthetic cannabinoid LC/Q-TOFMS Metabolism Potential postmortem redistribution
This work was supported by JSPS KAKENHI Grant Number 30700546.
- 4.Ji N, Takahashi M, Uemura N, Seto T, Fukaya H, Suzuki J, Yoshida M, Kusano M, Nakayama H, Zaitsu K, Ishii A, Moriyasu T, Nakae D (2015) Identification of N, N-bis(1-pentylindol-3-yl-carboxy)naphthylamine (BiPICANA) found in an herbal blend product in the Tokyo metropolitan area and its cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays. Forensic Toxicol 33(1):84–92. doi: 10.1007/s11419-014-0253-6 CrossRefGoogle Scholar
- 6.Huffman JW, Zengin G, Wu M-J, Lu J, Hynd G, Bushell K, Thompson ALS, Bushell S, Tartal C, Hurst DP, Reggio PH, Selley DE, Cassidy MP, Wiley JL, Martin BR (2005) Structure–activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB1 and CB2 receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB2 receptor agonists. Bioorg Med Chem 13(1):89–112. doi: 10.1016/j.bmc.2004.09.050 PubMedCrossRefGoogle Scholar
- 13.Hebert-Chatelain E, Reguero L, Puente N, Lutz B, Chaouloff F, Rossignol R, Piazza P-V, Benard G, Grandes P, Marsicano G (2014) Cannabinoid control of brain bioenergetics: exploring the subcellular localization of the CB1 receptor. Mol Metab 3(4):495–504. doi: 10.1016/j.molmet.2014.03.007 PubMedPubMedCentralCrossRefGoogle Scholar
- 14.Benard G, Massa F, Puente N, Lourenco J, Bellocchio L, Soria-Gomez E, Matias I, Delamarre A, Metna-Laurent M, Cannich A, Hebert-Chatelain E, Mulle C, Ortega-Gutierrez S, Martin-Fontecha M, Klugmann M, Guggenhuber S, Lutz B, Gertsch J, Chaouloff F, Lopez-Rodriguez ML, Grandes P, Rossignol R, Marsicano G (2012) Mitochondrial CB1 receptors regulate neuronal energy metabolism. Nature Neuroscience 15 (4):558-564. doi:http://www.nature.com/neuro/journal/v15/n4/abs/nn.3053.html#supplementary-information
- 15.Zaitsu K, Hayashi Y, Suzuki K, Nakayama H, Hattori N, Takahara R, Kusano M, Tsuchihashi H, Ishi A Metabolome disruption of the rat cerebrum induced by the acute toxic effects of the synthetic cannabinoid MAM-2201. Life Sciences. doi: 10.1016/j.lfs.2015.05.013Google Scholar
- 17.Huffman JW, Mabon R, Wu M-J, Lu J, Hart R, Hurst DP, Reggio PH, Wiley JL, Martin BR (2003) 3-Indolyl-1-naphthylmethanes: new cannabimimetic indoles provide evidence for aromatic stacking interactions with the CB1 cannabinoid receptor. Bioorg Med Chem 11(4):539–549. doi: 10.1016/S0968-0896(02)00451-0 PubMedCrossRefGoogle Scholar
- 18.Esaki H, Ohtaki R, Maegawa T, Monguchi Y, Sajiki H (2007) Novel Pd/C-catalyzed redox reactions between aliphatic secondary alcohols and ketones under hydrogenation conditions: application to H − D exchange reaction and the mechanistic study. J Org Chem 72(6):2143–2150. doi: 10.1021/jo062582u PubMedCrossRefGoogle Scholar
- 20.Zaitsu K, Katagi M, Kamata T, Kamata H, Shima N, Tsuchihashi H, Hayashi T, Kuroki H, Matoba R (2008) Determination of a newly encountered designer drug “p-methoxyethylamphetamine” and its metabolites in human urine and blood. Forensic Sci Int 177(1):77–84. doi: 10.1016/j.forsciint.2007.11.001 PubMedCrossRefGoogle Scholar