Analytical characterization of bioactive N-benzyl-substituted phenethylamines and 5-methoxytryptamines

  • Rapid Commun Mass Spectrom. 2015 Apr 15;29(7):573-84. doi: 10.1002/rcm.7134.
Simon D Brandt  1 ,  Simon P Elliott  2 ,  Pierce V Kavanagh  3 ,  Nicola M Dempster  1 ,  Markus R Meyer  4 ,  Hans H Maurer  4 ,  David E Nichols  5
Affiliations
  • 1. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
  • 2. ROAR Forensics, Malvern Hills Science Park, Geraldine Road, Malvern, WR14 3SZ, UK.
  • 3. Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin, 8, Ireland.
  • 4. Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany.
  • 5. Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Genetic Medicine Building, 120 Mason Farm Road, Chapel Hill, NC, 27599, USA.
PMID: 26212274 DOI: 10.1002/rcm.7134
Abstract

Rationale: Substances based on the N-(2-methoxybenzyl)phenethylamine template ('NBOMe' derivatives) play an important role in medicinal research but some of these derivatives have also appeared as 'research chemicals' for recreational use which has attracted attention worldwide. A major challenge associated with newly emerging substances includes the lack of analytical data and the ability to correctly identify positional isomers.

Methods: Six N-benzylphenethylamines based on the 2,5-dimethoxy-4-iodophenethylamine structure ('25I') and twelve substituted N-benzyl-5-methoxytryptamines ('5MT') have been prepared and extensively characterized. Techniques used for characterization were gas chromatography/ion trap mass spectrometry in electron and chemical ionization mode, liquid chromatography/diode array detection (DAD), infrared spectroscopy, electrospray high mass accuracy quadrupole time-of-flight tandem mass spectrometry, and triple quadrupole tandem mass spectrometry.

Results: The characterization of 18 'NBOMe' compounds provided a comprehensive collection of chromatographic and spectral data. Four groups of three positional isomers, i.e. 25I-NB2OMe, 25I-NB3OMe, 25I-NB4OMe, 25I-NB2B, 25I-NB3B, 25I-NB4B and their 5-methoxytryptamine counterparts, were included and assessed for ability to obtain differentiation. Six meta-substituted N-benzyl derivatives of 5-methoxytryptamine (CF3, F, CH3, Cl, I, SCH3) were also studied.

Conclusions: The implementation of mass spectral techniques was helpful for the differentiation between isomers, for example, when considering the difference in a number of ion ratios. This was considered beneficial in cases where chromatographic separation was only partially achieved under liquid chromatography (LC) conditions. The use of LC/DAD analysis was also found to be valuable for this particular purpose, which confirmed the integrative value of complementary techniques used in areas related to forensic toxicology.

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