title: First reported fatalities associated with the 'research chemical' 2-methoxydiphenidine.
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.
authors.affiliation: ROAR Forensics, Malvern Hills Science Park, Geraldine Road, Malvern WR14 3SZ, UK simontox@yahoo.co.uk.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Elliott
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: Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Wallach
authors.affiliation: Department of Anthropology, The New School for Social Research, 66 West 12th Street, New York, NY 10011, USA.
authors.forename: Hamilton
authors.initials: H
authors.lastname: Morris
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
mesh_terms: D000328:Adult; D000778:Anesthetics, Dissociative / Q000097:blood* / Q000506:poisoning*; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D010880:Piperidines / Q000097:blood* / Q000506:poisoning*; D011041:Poisoning / Q000097:blood
chemical_list: D000778:Anesthetics, Dissociative; D010880:Piperidines; C000595747:1-(1-(2-methoxyphenyl)-2-phenylethyl)piperidine