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First Reported Fatalities Associated with the 'Research Chemical' 2-Methoxydiphenidine

Simon Elliott, Simon D. Brandt, Jason Wallach, Hamilton Morris, Pierce V. Kavanagh

Journal of Analytical Toxicology February 19, 2015 DOI: 10.1093/jat/bkv006 via OpenAlex

Summary

2-Methoxydiphenidine (2-MXP), a dissociative research chemical sold as an alternative to methoxetamine and ketamine, was detected in post-mortem blood and urine from three fatalities. Femoral blood concentrations were 24.0, 2.0, and 1.36 mg/L; the lowest case had an alternative cause of death. Therapeutic levels of prescription drugs were also present. Metabolites included hydroxy-2-MXP (with hydroxylation on the piperidine ring), O-desmethyl-2-MXP, and hydroxylated O-desmethyl-2-MXP. Diphenidine and hydroxy-diphenidine were detected, but it was unclear if they came from 2-MXP or separate diphenidine use. These are the first published fatalities involving 2-MXP, providing analytical data for forensic toxicologists.

Study at a glance

Characteristics Case series Case report Peer reviewed
Sample size 3
Population Decedents with 2-MXP detected in post-mortem blood and urine
Keywords Desmethyl Metabolite Piperidine Stereochemistry Biochemistry
Citations 54
Key finding Three fatalities involved 2-MXP, with femoral blood concentrations of 24.0, 2.0, and 1.36 mg/L, and hydroxy-2-MXP was the main metabolite.

Abstract

2-Methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine, also known as 'MXP' or '2-MeO-diphenidine' (or 2-MXP), has been available as a 'research chemical' since 2013 as a purported alternative to the 'dissociative anesthetics' methoxetamine and ketamine. Three deaths which involved the detection of 2-MXP in post-mortem blood and urine were encountered in forensic casework. The 2-, 3- and 4-methoxyphenyl positional isomers were synthesized to confirm the identity and concentration of 2-MXP. The 2-MXP femoral blood concentrations in the cases were found to be 24.0, 2.0 and 1.36 mg/L (the latter with an alternative cause of death). Some additional prescription drugs were encountered at therapeutic concentrations in all three cases. Analysis of the biofluids allowed the detection and characterization of various metabolites, including the suggested presence of hydroxy-2-MXP as the main metabolite with the hydroxyl group located on the piperidine rather than the phenyl or benzyl moiety. Additional metabolites included O-desmethyl-2-MXP and hydroxylated O-desmethyl-2-MXP. Diphenidine and hydroxy-diphenidine, also showing the presence of the hydroxyl group on the piperidine ring, were also detected. It was not possible to identify whether these arose from 2-MXP biotransformation or whether they represented the presence of diphenidine as a separate substance. These are the first published fatalities involving 2-MXP and presents analytical data to assist analytical toxicologists with future casework.

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