title: Analytical characterization of bioactive N-benzyl-substituted phenethylamines and 5-methoxytryptamines.
abstract: BACKGROUND
  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.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Brandt
authors.affiliation: ROAR Forensics, Malvern Hills Science Park, Geraldine Road, Malvern, WR14 3SZ, UK.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Elliott
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin, 8, Ireland.
authors.forename: Pierce V
authors.initials: PV
authors.lastname: Kavanagh
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Dempster
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Meyer
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Genetic Medicine Building, 120 Mason Farm Road, Chapel Hill, NC, 27599, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Nichols
mesh_terms: D008735:5-Methoxytryptamine / Q000032:analysis* / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007536:Isomerism; D008958:Models, Molecular; D010627:Phenethylamines / Q000032:analysis* / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D010627:Phenethylamines; D008735:5-Methoxytryptamine