Analytical characterization of three hallucinogenic N-(2-methoxy)benzyl derivatives of the 2C-series of phenethylamine drugs Dariusz Zuba* and Karolina Sekula This publication reports analytical properties of three new hallucinogenic substances identified in blotter papers seized from the drug market, namely 25D-NBOMe [2-(2,5-dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine], 25E-NBOMe [2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine] and 25G-NBOMe [2-(2,5-dimethoxy-3,4-dimethylphenyl)-N- (2-methoxybenzyl)ethanamine]. These substances are N-(2-methoxy)benzyl derivatives of the 2C-series of phenethylamine drugs. The applied procedure covered a variety of analytical methods, including gas chromatography with electron impact mass spectrometry (GC-EI-MS; without derivatization and after derivatization with trifluoroacetic anhydride (TFAA)), liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry (LC-ESI-QTOF-MS), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR), which made it possible to identify the active components unequivocally. The GC-MS spectra of analyzed compounds were very similar, with dominant ions observed at m/z = 150, 121, and 91. The remaining ions were analogous to those observed for parent substances, namely 2C-D, 2C-E, 2C-G, but their inten- sities were low. Derivatization allowed determination of molecular masses of the investigated substances. Their exact masses and chemical formulas were confirmed by LC-QTOF-MS experiments and the fragmentation patterns of these compounds following ESI were determined. The tandem mass spectrometry (MS/MS) experiments confirmed that the studied substances were N-(2-methoxy)benzyl derivatives of the 2C-series compounds. Final elucidation of the structures was performed by NMR spectroscopy. The substances were also characterized by FTIR spectroscopy to corroborate the identity of the compounds. Copyright © 2012 John Wiley & Sons, Ltd. Keywords: hallucinogens; identification; blotter paper; NBOMe Introduction In recent years, a number of new substances have been marketed. They have been usually advertised as safe and legal analogues of controlled drugs, having similar psychoactive action. Although two new chemical classes of drugs, namely cathinones and piperazines, were the most popular in the last four years (2008–2011), several representatives of ‘old’ classes – phenethylamines and tryptamines – were also detected in this period. [1–9] Hallucinogenic substances belonging to these chemical families were extensively marketed in Poland especially in the last months. The significant increase in the popularity of hallucinogens was surprising, because few representatives were seized on the Polish drug market in the previous 10 years. Agonist activity at the serotonin (5-hydroxytryptamine) recep- tor subtype 2A (5-HT 2A ) is essential for the psychopharmacology of psychedelic substances such as lysergic acid diethylamide (LSD), mescalin and psilocin; i.e. compounds with unique and dramatic effects on certain aspects of consciousness. [10] Starting from the 1990s, intensive studies on the affinity of different substances for serotonin receptors have been performed. Structure-activity relationship (SAR) studies have led to agents with low nanomolar affinities for the 5-HT 2A receptor, some of which are among the most potent partial agonists with hallucino- genic effects known to date. [11–14] It was found that derivatives of phenethylamine containing two methoxy groups substituted at positions 2 and 5 of the benzene ring interact effectively with serotonin receptors, and the majority act as agonists of the 5-HT 2A receptor. This group of substances was named by Alexander Shulgin as the 2C family. He synthesized many repre- sentatives and described their action on the body in the book PIHKAL, Phenethylamines I Have Known And Loved. [15] Typically, a 2C-series member carries a lipophilic substituent in the para position relative to the side chain, which further enhances the 5-HT 2A affinity and partial agonistic activity. [16–22] The most active compounds identified to date possess an ether, alkylthio, alkyl, or halogen group at this position and potency increases in the aforementioned sequence. [22–24] The popular representatives were: 2C-B (4-bromo-2,5-dimethoxy-b-phenethylamine), 2C-I (4-iodo-2,5-dimethoxy-b-phenethylamine), 2C-T-2 (4-ethylthio- 2,5-dimethoxy-b-phenethylamine) and 2C-T-7 (2,5-dimethoxy- 4-propylthio-b-phenethylamine). [25–27] In the last few years, 2C-C (4-chloro-2,5-dimethoxy-b-phenethylamine), 2C-D (2,5-dimethoxy- 4-methyl-b-phenethylamine), 2C-E (4-ethyl-2,5-dimethoxy-b- phenethylamine), 2C-P (2,5-dimethoxy-4-propyl-b-phenethylamine), 2C-N (2,5-dimethoxy-4-nitro-b-phenethylamine) and 2C-G (2,5-dimethoxy-3,4-dimethyl-b-phenethylamine) have appeared on the market. [28–30] 2C-G is an untypical member of this group, * Correspondence to: Dariusz Zuba, Institute of Forensic Research, Department of Forensic Toxicology, Westerplatte 9, 31033 Kraków, Poland. E-mail: dzuba@ies.krakow.pl Institute of Forensic Research, Department of Forensic Toxicology, Kraków, Poland Drug Test. Analysis (2012) Copyright © 2012 John Wiley & Sons, Ltd. Research article Drug Testing and Analysis Received: 26 May 2012 Revised: 3 July 2012 Accepted: 3 July 2012 Published online in Wiley Online Library (www.drugtestinganalysis.com) DOI 10.1002/dta.1397