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. Copyright © 2015 John Wiley & Sons, Ltd.

Return of the lysergamides. Part I: Analytical and behavioural characterization of 1‐propionyl‐d‐lysergic acid diethylamide (1P‐LSD)

“…A potential alternative for m/z 279.14899 might have involved the loss of N , N ‐diethylamine (C 4 H 11 N) from the protonated molecule to give m/z 307.14283 (C 19 H 19 N 2 O 2 + ) followed cleavage of CO (Figure 5A4). As previously demonstrated with the detection of the new psychoactive substance 2‐methoxydiphenidine (MXP) from a tablet surface, the analysis of a 1P‐LSD blotter by matrix‐assisted ionization inlet Orbitrap mass spectrometry provided mass spectral information that agreed with those detected under QTOF‐MS/MS conditions (Supporting Information). An additional ESI triple quadrupole tandem mass spectrum was added as Supporting Information that also showed comparable product ions.…”

Analytical characterization of N,N‐diallyltryptamine (DALT) and 16 ring‐substituted derivatives

“…One of the challenges that might be encountered when identifying a new psychoactive substance on the market includes the consideration of potential isomers, especially if not all of these substances are commercially available for analytical comparisons. From this perspective, it has become increasingly helpful to consider supporting implementation of analytical procedures by synthesis of the isomers of interest to support the verification process . Figure shows the similarity of EI mass spectra recorded for 5‐F‐DALT ( 10 ) and 6‐F‐DALT ( 15 ).…”

Syntheses and analytical characterizations of the research chemical 1‐[1‐(2‐fluorophenyl)‐2‐phenylethyl]pyrrolidine (fluorolintane) and five of its isomers

“…The reactions generally utilize convenient low‐cost reagents to produce final compounds in moderate to excellent yields. This method was utilized previously to prepare other 1,2‐diarylethylamines such as 2‐MXP and 2‐Cl‐DPP and a range of other diphenidine analogs . Finally, during final preparation of HCl salts, it was noticed via NMR that these crystals can form solvate co‐crystals with methanol, ethanol, and isopropanol to differing degrees which led to the decision to employ acetone as the recrystallization solvent.…”