Skip to main content
SpringerLink
Log in

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

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

A Publisher's Erratum to this article was published on 30 December 2015

This article has been updated

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Change history

  • 30 December 2015

    Erratum to: Int J Legal Med (2015) 129:1233–1245

References

  1. Tai S, Fantegrossi W (2014) Synthetic cannabinoids: pharmacology, behavioral effects, and abuse potential. Current Addict Rep 1(2):129–136. doi:10.1007/s40429-014-0014-y

    Article  Google Scholar 

  2. ElSohly MA, Gul W, Wanas AS, Radwan MM (2014) Synthetic cannabinoids: analysis and metabolites. Life Sciences 97(1):78–90. doi:10.1016/j.lfs.2013.12.212

    Article  PubMed  CAS  Google Scholar 

  3. Kikura-Hanajiri R, Uchiyama N, Kawamura M, Goda Y (2013) Changes in the prevalence of synthetic cannabinoids and cathinone derivatives in Japan until early 2012. Forensic Toxicol 31(1):44–53. doi:10.1007/s11419-012-0165-2

    Article  Google Scholar 

  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

    Article  Google Scholar 

  5. Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA (2014) Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug and Alcohol Dependence 144:12–41. doi:10.1016/j.drugalcdep.2014.08.005

    Article  PubMed  CAS  Google 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

    Article  PubMed  CAS  Google Scholar 

  7. Kneisel S, Auwärter V (2012) Analysis of 30 synthetic cannabinoids in serum by liquid chromatography-electrospray ionization tandem mass spectrometry after liquid-liquid extraction. J Mass Spectrom 47(7):825–835. doi:10.1002/jms.3020

    Article  PubMed  CAS  Google Scholar 

  8. Saito T, Namera A, Miura N, Ohta S, Miyazaki S, Osawa M, Inokuchi S (2013) A fatal case of MAM-2201 poisoning. Forensic Toxicol 31(2):333–337. doi:10.1007/s11419-013-0190-9

    Article  Google Scholar 

  9. Patton AL, Chimalakonda KC, Moran CL, McCain KR, Radominska-Pandya A, James LP, Kokes C, Moran JH (2013) K2 toxicity: fatal case of psychiatric complications following AM2201 exposure. J Forensic Sci 58(6):1676–1680. doi:10.1111/1556-4029.12216

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Hermanns-Clausen M, Kneisel S, Hutter M, Szabo B, Auwärter V (2013) Acute intoxication by synthetic cannabinoids – Four case reports. Drug Test Anal 5(9-10):790–794. doi:10.1002/dta.1483

    Article  PubMed  CAS  Google Scholar 

  11. Hermanns-Clausen M, Kneisel S, Szabo B, Auwärter V (2013) Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction 108(3):534–544. doi:10.1111/j.1360-0443.2012.04078.x

    Article  PubMed  Google Scholar 

  12. K-i T, Funada M (2014) Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death. Toxicol Appl Pharmacol 274(1):17–23. doi:10.1016/j.taap.2013.10.028

    Article  Google 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

    Article  PubMed  CAS  PubMed Central  Google 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.2015.05.013

  16. Fantegrossi WE, Moran JH, Radominska-Pandya A, Prather PL (2014) Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ9-THC: mechanism underlying greater toxicity? Life Sciences 97(1):45–54. doi:10.1016/j.lfs.2013.09.017

    Article  PubMed  CAS  PubMed Central  Google 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

    Article  PubMed  CAS  Google 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

    Article  PubMed  CAS  Google Scholar 

  19. Zaitsu K, Katagi M, Kamata HT, Kamata T, Shima N, Miki A, Tsuchihashi H, Mori Y (2009) Determination of the metabolites of the new designer drugs bk-MBDB and bk-MDEA in human urine. Forensic Sci Int 188(1–3):131–139. doi:10.1016/j.forsciint.2009.04.001

    Article  PubMed  CAS  Google 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

    Article  PubMed  CAS  Google Scholar 

  21. Hopfgartner G, Tonoli D, Varesio E (2012) High-resolution mass spectrometry for integrated qualitative and quantitative analysis of pharmaceuticals in biological matrices. Anal Bioanal Chem 402(8):2587–2596. doi:10.1007/s00216-011-5641-8

    Article  PubMed  CAS  Google Scholar 

  22. Pélissier-Alicot A-L, Gaulier J-M, Champsaur P, Marquet P (2003) Mechanisms underlying postmortem redistribution of drugs: a review. J Anal Toxicol 27(8):533–544. doi:10.1093/jat/27.8.533

    Article  PubMed  Google Scholar 

  23. Harris CR, Brown A (2013) Synthetic cannabinoid intoxication: a case series and review. J Emerg Med 44(2):360–366. doi:10.1016/j.jemermed.2012.07.061

    Article  PubMed  Google Scholar 

  24. Young AC, Schwarz E, Medina G, Obafemi A, Feng S-Y, Kane C, Kleinschmidt K (2012) Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation. Am J Emerg Med 30(7):1320.e1325–1320.e1327. doi:10.1016/j.ajem.2011.05.013

    Article  Google Scholar 

  25. Jang M, Shin I, Yang W, Chang H, Yoo HH, Lee J, Kim E (2014) Determination of major metabolites of MAM-2201 and JWH-122 in in vitro and in vivo studies to distinguish their intake. Forensic Sci Int 244:85–91. doi:10.1016/j.forsciint.2014.08.008

    Article  PubMed  CAS  Google Scholar 

  26. Sobolevsky T, Prasolov I, Rodchenkov G (2012) Detection of urinary metabolites of AM-2201 and UR-144, two novel synthetic cannabinoids. Drug Test Anal 4(10):745–753. doi:10.1002/dta.1418

    Article  PubMed  CAS  Google Scholar 

  27. Hutter M, Moosmann B, Kneisel S, Auwärter V (2013) Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism. J Mass Spectrom 48(7):885–894. doi:10.1002/jms.3229

    Article  PubMed  CAS  Google Scholar 

  28. Jang M, Yang W, Shin I, Choi H, Chang H, Kim E (2014) Determination of AM-2201 metabolites in urine and comparison with JWH-018 abuse. Int J Legal Med 128(2):285–294. doi:10.1007/s00414-013-0884-x

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by JSPS KAKENHI Grant Number 30700546.

Author information

Authors and Affiliations

  1. Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine, 65 tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Kei Zaitsu, Hiroshi Nakayama, Mayumi Yamanaka, Kazuaki Hisatsune, Kentaro Taki, Tomomi Asano, Maiko Kusano, Hitoshi Tsuchihashi & Akira Ishii

  2. Forensic Science Laboratory, Aichi Prefectural Police Headquarters, 2-1-1Sannomaru, Naka-ku, Nagoya, 460-8502, Japan

    Kazuaki Hisatsune

  3. Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18 Hommachi, Chuo-ku, Osaka, 541-0053, Japan

    Tooru Kamata & Munehiro Katagai

  4. Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-8673, Japan

    Yumi Hayashi

Authors
  1. Kei Zaitsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mayumi Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazuaki Hisatsune
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kentaro Taki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomomi Asano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tooru Kamata
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Munehiro Katagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yumi Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maiko Kusano
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hitoshi Tsuchihashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Akira Ishii
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kei Zaitsu.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 29 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zaitsu, K., Nakayama, H., Yamanaka, M. et al. 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. Int J Legal Med 129, 1233–1245 (2015). https://doi.org/10.1007/s00414-015-1257-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-015-1257-4

Keywords

Search

Navigation