Methoxpropamine (MXPr) in powder, urine and hair samples: Analytical characterization and metabolite identification of a new threat.

Methoxpropamine (MXPr) is an arylcyclohexylamine dissociative drug with structural similarities with 3-MeO-PCE, ketamine and deschloroketamine. MXPr was identified for the first time in Europe in October 2019 in Denmark and is considered a new psychoactive substance. We undertook the molecular identification and characterization of MXPr in urine, hair and powder samples. We used a combination of several analytical methods: liquid-state nuclear magnetic resonance (NMR), infra-red spectroscopy (IR) and liquid chromatography high-resolution mass spectrometry (LC-HRMS). The second objective was to explore the metabolism of MXPr in silico and in vitro. To detect characteristic metabolites that prove 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 (Unifi®) was used to predict in silico biotransformations of MXPr. Three metabolites were identified in the in vitro studies including N-despropyl(nor)MXPr, O-desmethyl MXPr and dihydroMXPr. Most of these phase II metabolites were confirmed to be present in urine and hair samples collected from an MXPr consumer. This is the first report of the identification of MXPr in France with analytical findings. This study highlights the challenge of identifying new psychoactive substances (NPS) when they are missing from compound libraries and if a standard is not available. The use of various complementary analytical methods combined with HRMS offers a promising approach for the molecular characterization of NPS.

Prevalence of new psychoactive substances and prescription drugs in the Belgian driving under the influence of drugs population.

Driving under the influence of drugs (DUID) is a worldwide problem. Several countries have adopted DUID legislations which prove their deterrent effect and impact on road safety. However, the use of new psychoactive substances (NPS) and prescription drugs is not known, as the applied roadside screening tests have not yet been adapted for these compounds. In this study, 558 blood samples obtained during roadside controls in Belgium (January to August 2015) after a positive Drugwipe 5S® test and 199 oral fluid (OF) samples obtained from negatively screened test pads were analyzed. The NPS positivity rate was 7% in blood, while it reached 11% in OF. NPS detected were: diphenidine, ketamine, 4-fluoroamphetamine, 2-amino-indane, methoxetamine, α-PVP, methiopropamine, a mix of 5-MAPB/5-EAPB, TH-PVP, mephedrone, methedrone, 4-methylethylcathinone, 5-MeO-DALT, 4-Acetoxy-DiPT, AB Fubinaca, FUB-JWH018, JWH020, trifluoromethylphenylpiperazine, and ethylphenidate. Moreover, 17% of blood samples (and 5% of OF) contained an analgesic drug, 10% (0.5%) a benzodiazepine/hypnotic, 5% (2%) an antidepressant, 2% (3%) an antipsychotic, 2% an antiepileptic drug, and 1% methylphenidate. The presence of NPS in the young (and predominately male) DUID population is proven. Furthermore, a high level of poly-drug use including combinations of NPS, licit, and drugs of abuse was observed. Further research concerning the development of on-site NPS detection techniques should be established. Meanwhile, the effects of combined drug use on driving ability and the physical/psychological signs after NPS use should be performed to improve the on-site DUID detection of NPS by police officers, so they can engage in blood sampling for a general unknown screening.

Ameliorative effect of vitamin C against hepatotoxicity induced by emamectin benzoate in rats.

In the present study, we aimed to assess the potential protective effect of ascorbic acid (AA) against emamectin benzoate (EMB)-induced hepatotoxicity. For this purpose, biochemical, histopathological and analytical investigations were performed. Male Wistar rats were distributed into three groups, that is, a control group, an EMB group given 10 mg EMB/kg body weight (BW) by gavage and an EMB + AA group given 10 mg EMB/kg BW and vitamin C intraperitoneally (200 mg/kg). The duration of the treatment was 28 days and the duration of the study was 42 days. There was a statistically significant increase of all hepatic biomarkers, that is, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase activities, and glycemia, in EMB-treated group when compared with the control group. Light microscopic observations revealed variable signs of hepatotoxicity in the EMB group, which were represented by alteration of normal hepatic architecture, inflammatory cell infiltration, hepatocellular steatosis and foci of necrosis at 28 and 42 days post-treatment. However, co-treatment with vitamin C reduced EMB-related liver toxicity and diminished the abnormal biochemical and architectural damage. Emamectin B1a and B1b residues were detectable in all plasma samples of treated rats at 14, 21 and 28 days of treatment. The drug liver tissue concentration was significantly lower in EMB + AA group compared with EMB group at 28 and 42 days. In conclusion, the findings of the present study clearly indicate a significant protective action of vitamin C against EMB hepatotoxicity.

Acute Methiopropamine Intoxication After "Synthacaine" Consumption.

Use of methiopropamine (MPA), a synthetic metamfetamine analog, has been detected since 2011 in Europe, but there is limited information on its acute toxicity. A 30-year-old man was admitted to the emergency department in a confused state, with paranoid delusion, auditory and visual hallucinatory experiences, and incoherent speech following the use of "synthacaine" (a slang term derived from "synthetic" and "cocaine"). Toxicological screening for pharmaceuticals and drugs of abuse by liquid chromatography-diode-array detector, gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS-MS) detected MPA, which was subsequently quantified by a specific LC-MS-MS method. Of note, 13 h after presentation to the emergency department, the plasma concentration of MPA was 14 ng/mL. This case report confirms the toxicity of MPA and the need for toxicological analysis to confirm the substance actually ingested by users of new psychoactive substances.