title: Test purchase, synthesis, and characterization of 2-methoxydiphenidine (MXP) and differentiation from its meta- and para-substituted isomers.
abstract: The structurally diverse nature of the 1,2-diphenylethylamine template provides access to a range of substances for drug discovery work but some have attracted attention as 'research chemicals'. The most recent examples include diphenidine, i.e. 1-(1,2-diphenylethyl)piperidine and 2-methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine (MXP, methoxyphenidine, 2-MXP) that have been associated with uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist activity. Analytical challenges encountered during chemical analysis include the presence of positional isomers. Three powdered samples suspected to contain 2-MXP were obtained from three Internet retailers in the United Kingdom and subjected to analytical characterization by gas chromatography (GC) and high performance liquid chromatography (HPLC) coupled to various forms of mass spectrometry (MS). Nuclear magnetic resonance spectroscopy, infrared spectroscopy and thin layer chromatography were also employed. This was supported by the synthesis of all three isomers (2-, 3- and 4-MXP) by two different synthetic routes. The analytical data obtained for the three purchased samples were consistent with the synthesized 2-MXP standard and the differentiation between the isomers was possible. Distinct stability differences were observed for all three isomers during in-source collision-induced dissociation of the protonated molecule when employing detection under HPLC selected-ion monitoring detection, which added to the ability to differentiate between them. Furthermore, the analysis of a 2-MXP tablet by matrix assisted inlet ionization Orbitrap mass spectrometry confirmed that it was possible to detect the protonated molecule of 2-MXP directly from the tablet surface following addition of 3-nitrobenzonitrile as the matrix.
authors: Department of Life and Physical Sciences, School of Science, Athlone Institute of Technology, Dublin Road, Westmeath, Ireland.|Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin, 8, Ireland.
authors: Gavin
authors: G
authors: McLaughlin
authors: Department of Life and Physical Sciences, School of Science, Athlone Institute of Technology, Dublin Road, Westmeath, Ireland.
authors: Noreen
authors: N
authors: Morris
authors: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin, 8, Ireland.
authors: Pierce V
authors: PV
authors: Kavanagh
authors: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin, 8, Ireland.
authors: John D
authors: JD
authors: Power
authors: School of Chemistry, Trinity College, Dublin, 2, Ireland.
authors: John
authors: J
authors: O'Brien
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College, Dublin, 2, Ireland.
authors: Brian
authors: B
authors: Talbot
authors: ROAR Forensics, Malvern Hills Science Park, Geraldine Road, WR14 3SZ, UK.
authors: Simon P
authors: SP
authors: Elliott
authors: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, 19104, USA.
authors: Jason
authors: J
authors: Wallach
authors: Department of Chemistry and Biochemistry, University of the Sciences, Philadelphia, PA, 19104, USA.
authors: Khoa
authors: K
authors: Hoang
authors: The New School for Social Research, Department of Anthropology, 66 West 12th Street, NY, 10011, New York, USA.
authors: Hamilton
authors: H
authors: Morris
authors: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors: Simon D
authors: SD
authors: Brandt
mesh_terms: D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D007536:Isomerism; D010880:Piperidines / Q000737:chemistry* / Q000302:isolation & purification; D011619:Psychotropic Drugs / Q000737:chemistry* / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization; D013607:Tablets
chemical_list: D010880:Piperidines; D011619:Psychotropic Drugs; D013607:Tablets; C000595747:1-(1-(2-methoxyphenyl)-2-phenylethyl)piperidine; C000599677:diphenidine
keywords: 1,2-diphenylethylamines; diphenidine; methoxyphenidine; new psychoactive substances; ‘research chemicals’