Forensic Toxicology

, Volume 31, Issue 2, pp 292–300 | Cite as

Mass spectrometric differentiation of the isomers of mono-methoxyethylamphetamines and mono-methoxydimethylamphetamines by GC–EI–MS–MS

  • Kei Zaitsu
  • Haruhiko Miyagawa
  • Yuki Sakamoto
  • Shuntaro Matsuta
  • Kento Tsuboi
  • Hiroshi Nishioka
  • Munehiro Katagi
  • Takako Sato
  • Michiaki Tatsuno
  • Hitoshi Tsuchihashi
  • Koichi Suzuki
  • Akira Ishii
Original Article

Abstract

Mass spectrometric differentiation of the six isomers of mono-methoxyethylamphetamines (MeO-EAs) and mono-methoxydimethylamphetamines (MeO-DMAs) by gas chromatography–electron ionization–tandem mass spectrometry (GC–EI–MS–MS) was investigated. Based on their EI-mass spectra, the fragment ions at m/z 121 and 72 were selected as precursor ions for their regioisomeric and structurally isomeric differentiation, respectively. Collision-induced dissociation provides intensity differences in product ions among the isomers, enabling mass spectrometric differentiation of the isomers. Furthermore, high reproducibility of the product ion spectra at the optimized collision energy was confirmed, demonstrating the reliability of the method. To our knowledge, this is the first report on mass spectrometric differentiation of the six isomers of MeO-EAs and MeO-DMAs by GC–EI–MS–MS. Isomeric differentiation by GC–EI–MS–MS has a high potential to discriminate isomers of newly encountered designer drugs, making GC–MS–MS a powerful tool in the forensic toxicology field.

Keywords

GC–EI–MS–MS Isomeric differentiation Methoxyethylamphetamine Methoxydimethylamphetamine Designer drugs 

Notes

Conflict of interest

There are no financial or other relations that could lead to a conflict of interest.

References

  1. 1.
    Nakajima J, Takahashi M, Seto T, Kanai C, Suzuki J, Yoshida M, Hamano T (2011) Identification and quantitation of two benzoylindoles AM-694 and (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone, and three cannabimimetic naphthoylindoles JWH-210, JWH-122, and JWH-019 as adulterants in illegal products obtained via the Internet. Forensic Toxicol 29(2):95–110CrossRefGoogle Scholar
  2. 2.
    Nakajima J, Takahashi M, Nonaka R, Seto T, Suzuki J, Yoshida M, Kanai C, Hamano T (2011) Identification and quantitation of a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone and a naphthoylindole 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201) found in illegal products obtained via the Internet and their cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays. Forensic Toxicol 29(2):132–141CrossRefGoogle Scholar
  3. 3.
    Namera A, Nakamoto A, Saito T, Nagao M (2011) Colorimetric detection and chromatographic analyses of designer drugs in biological materials: a comprehensive review. Forensic Toxicol 29(1):1–24CrossRefGoogle Scholar
  4. 4.
    Zaitsu K, Katagi M, Tatsuno M, Sato T, Tsuchihashi H, Suzuki K (2011) Recently abused β-keto derivatives of 3,4-methylenedioxyphenylalkylamines: a review of their metabolisms and toxicological analysis. Forensic Toxicol 29(2):73–84CrossRefGoogle Scholar
  5. 5.
    Nakajima J, Takahashi M, Seto T, Yoshida M, Kanai C, Suzuki J, Hamano T (2012) Identification and quantitation of two new naphthoylindole drugs-of-abuse, (1-(5-hydroxypentyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone (AM-2202) and (1-(4-pentenyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone, with other synthetic cannabinoids in unregulated “herbal” products circulated in the Tokyo area. Forensic Toxicol 30(1):33–44CrossRefGoogle Scholar
  6. 6.
    Uchiyama N, Matsuda S, Wakana D, Kikura-Hanajiri R, Goda Y (2013) New cannabimimetic indazole derivatives, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA) and N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA) identified as designer drugs in illegal products. Forensic Toxicol 31(1):93–100CrossRefGoogle Scholar
  7. 7.
    Park Y, Lee C, Lee H, Pyo J, Jo J, Lee J, Choi H, Kim S, Hong R, Park Y, Hwang B, Choe S, Jung J (2013) Identification of a new synthetic cannabinoid in a herbal mixture: 1-butyl-3-(2-methoxybenzoyl)indole. Forensic Toxicol 1:1–10Google Scholar
  8. 8.
    Dean B, Stellpflug S, Burnett A, Engebretsen K (2013) 2C or not 2C: phenethylamine designer drug review. J Med Toxicol 9:1–7Google Scholar
  9. 9.
    Strano-Rossi S, Anzillotti L, Castrignanò E, Romolo FS, Chiarotti M (2012) Ultra high performance liquid chromatography–electrospray ionization–tandem mass spectrometry screening method for direct analysis of designer drugs, “spice” and stimulants in oral fluid. J Chromatogr A 1258:37–42PubMedCrossRefGoogle Scholar
  10. 10.
    Grabenauer M, Krol WL, Wiley JL, Thomas BF (2012) Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: implications for nontargeted screening of designer drugs. Anal Chem 84(13):5574–5581PubMedCrossRefGoogle Scholar
  11. 11.
    EMCDDA (2003) Report on the risk assessment of PMMA in the framework of the joint action on new synthetic drugs. Publications Office of the European Union, LuxembourgGoogle Scholar
  12. 12.
    Zaitsu K, Katagi M, Kamata H, Kamata T, Shima N, Miki A, Iwamura T, Tsuchihashi H (2008) Discrimination and identification of the six aromatic positional isomers of trimethoxyamphetamine (TMA) by gas chromatography–mass spectrometry (GC–MS). J Mass Spectrom 43(4):528–534PubMedCrossRefGoogle Scholar
  13. 13.
    Zaitsu K, Katagi M, Kamata H, Miki A, Tsuchihashi H (2008) Discrimination and identification of regioisomeric β-keto analogues of 3,4-methylenedioxyamphetamines by gas chromatography–mass spectrometry. Forensic Toxicol 26(2):45–51CrossRefGoogle Scholar
  14. 14.
    Belal T, Awad T, DeRuiter J, Clark CR (2008) GC–MS studies on acylated derivatives of 3-methoxy-4-methyl- and 4-methoxy-3-methyl-phenethylamines: regioisomers related to 3,4-MDMA. Forensic Sci Int 178(1):61–82PubMedCrossRefGoogle Scholar
  15. 15.
    Awad T, DeRuiter J, Clark CR (2005) GC–MS analysis of acylated derivatives of the side chain and ring regioisomers of methylenedioxymethamphetamine. J Chromatogr Sci 43(6):296–303PubMedCrossRefGoogle Scholar
  16. 16.
    Clark CR, DeRuiter J, Noggle FT (1996) Chromatographic and mass spectrometry methods for the differentiation of N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine from regioisomeric derivatives. J Chromatogr Sci 34(5):230–237CrossRefGoogle Scholar
  17. 17.
    Aalberg L, DeRuiter J, Noggle FT, Sippola E, Clark CR (2003) Chromatographic and spectroscopic methods of identification for the side-chain regioisomers of 3,4-methylenedioxyphenethylamines related to MDEA, MDMMA, and MBDB. J Chromatogr Sci 41(5):227–233PubMedCrossRefGoogle Scholar
  18. 18.
    Nakazono Y, Tsujikawa K, Kuwayama K, Kanamori T, Iwata Y, Miyamoto K, Kasuya F, Inoue H (2013) Differentiation of regioisomeric fluoroamphetamine analogs by gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry. Forensic Toxicol 1:1–10Google Scholar
  19. 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):131–139PubMedCrossRefGoogle Scholar
  20. 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):77–84PubMedCrossRefGoogle Scholar
  21. 21.
    Westphal F, Rosner P, Junge T (2010) Differentiation of regioisomeric ring-substituted fluorophenethylamines with product ion spectrometry. Forensic Sci Int 194(1–3):53–59PubMedCrossRefGoogle Scholar
  22. 22.
    Borth S, Hänsel W, Rösner P, Junge T (2000) Regioisomeric differentiation of 2,3- and 3,4-methylenedioxy ring-substituted phenylalkylamines by gas chromatography/tandem mass spectrometry. J Mass Spectrom 35(6):705–710PubMedCrossRefGoogle Scholar
  23. 23.
    Borth S, Hänsel W, Rösner P, Junge T (2000) Synthesis of 2,3- and 3,4-methylenedioxyphenylalkylamines and their regioisomeric differentiation by mass spectral analysis using GC–MS–MS. Forensic Sci Int 114(3):139–153PubMedCrossRefGoogle Scholar
  24. 24.
    Katagi M, Tsutsumi H, Miki A, Nakajima K, Tsuchihashi H (2002) Analyses of clandestine tablets of amphetamines and their related designer drugs encountered in recent Japan. Jpn J Forensic Toxicol 20:303–319Google Scholar
  25. 25.
    McLafferty FWTF (1993) Interpretation of mass spectra, 4th edn. University Science Books, Mill ValleyGoogle Scholar
  26. 26.
    McLafferty FW (1957) Mass spectrometric analysis…aliphatic ethers. Anal Chem 29(12):1782–1789CrossRefGoogle Scholar
  27. 27.
    Rösner P, Junge T (1996) Investigation of the alkylamino group of aliphatic and arylaliphatic amines by collision-induced dissociation mass spectra ofC4H10 N + immonium ions. J Mass Spectrom 31(9):1047–1053CrossRefGoogle Scholar
  28. 28.
    Bowen RD (1991) The chemistry of CnH2n + 2 N + ions. Mass Spectrom Rev 10(3):225–279CrossRefGoogle Scholar
  29. 29.
    Bowen RD (1989) Reactions of isolated organic ions. Alkene loss from the immonium ions CH3CH=N + HC2H5 and CH3CH=N + HC3H7. J Chem Soc Perkin Trans 20(7):913–918Google Scholar

Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan 2013

Authors and Affiliations

  • Kei Zaitsu
    • 1
  • Haruhiko Miyagawa
    • 2
  • Yuki Sakamoto
    • 2
  • Shuntaro Matsuta
    • 3
  • Kento Tsuboi
    • 4
  • Hiroshi Nishioka
    • 3
  • Munehiro Katagi
    • 3
  • Takako Sato
    • 4
  • Michiaki Tatsuno
    • 3
  • Hitoshi Tsuchihashi
    • 4
  • Koichi Suzuki
    • 4
  • Akira Ishii
    • 1
  1. 1.Department of Legal Medicine and BioethicsNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Shimadzu CorporationKyotoJapan
  3. 3.Forensic Science Laboratory, Osaka Prefectural Police HeadquartersOsakaJapan
  4. 4.Department of Legal MedicineOsaka Medical CollegeTakatsukiJapan

Personalised recommendations