Identification and analytical characterization of recently emerged methoxpropamine (MXPr) in product and human urine samples

Abstract

Methoxpropamine (MXPr or 3-MeO-2’-oxo-PCPr) is an arylcyclohexylamine dissociative drug and a higher homologue of methoxetamine (MXE) with structural similarities with ketamine, deschloroketamine and 3-MeO-PCE. MXPr first identification in Europe was in decembre 2019 in Danemark. This study reports the first case of MXPr identification in France with analytical findings. The aim of this study was to identify and characterize MXPr in biological sample and product sample by combination of several analytical methods: 1 H NMR spectroscopy, IR spectroscopy, GC-MS and LC-HRMS. The secondary objective was to explore MXPr in silico and in vitro metabolism. Urine sample was submitted to toxicological analysis. A qualitative analysis was performed by GC-MS and LC-HRMS. Structural identification and purity were assessed using 1 H NMR spectroscopy, IR spectroscopy and LC-HRMS. To detect characteristic metabolites suitable for a proof of MXPr consumption by urine analysis, pooled human liver microsome (pHLM) assays were performed and evaluated using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS). A software algorithm (MetaboLynx) was used in order to predict in-silico biotransformations (Waters, Manchester, UK). Eight months later, hair sample was submitted to novel toxicological analysis. A 26-year-old man known as a polydrug addict especially new psychoactive substance (NPS) was admitted at emergency department. Patient was asymptomatic and urine immunochemistry screening for classic psychoactive substances was negative. LC-HRMS Screening identified oxazepam, nordiazepam, buprenorphine metabolite, N-ethylhexedrone and an unknown peak not found in all large libraries available. 1 H NMR product analysis showed the presence of MXPr with a purity of 95%. Structural identification was confirmed by IR spectroscopy. After the addition of this NPS to our library, retrospective urine analysis enabled the identification of the unknown peak as MXPr. This study highlights the difficulty of identifying some NPS when they are missing from the library and the product is not available. The use of various complementary analytical methods with high-resolution mass spectrometry appears to be necessary.