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

Goncalves, Ruben; Castaing, Nadège; Richeval, Camille; Ducint, Dominique; Titier, Karine; Morvan, Estelle; Grélard, Axelle; Loquet, Antoine; Molimard, Mathiéu

doi:10.1016/j.forsciint.2022.111215

Cited by 7 publications

(5 citation statements)

References 24 publications

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“…MXPr was generally excreted as parent drug within the 24 h. Table 2 shows the approximate MXPr concentrations detected in the various urine samples. The identification of the main phase I metabolites is in agreement with the study by Goncalves et al, 21 which confirmed the presence of most of the phase II metabolites in urine collected from an MXPr consumer. The MXPr pharmacokinetcs profile shows an excretion peak after 1 h, then a progressive decay along 6 to 12 h, even if MXPr is still detectable 24 h after administration of 3 and 10 mg/kg.…”

Section: Resultssupporting

confidence: 91%

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Metabolic study of new psychoactive substance methoxpropamine in mice by UHPLC‐QTOF‐HRMS

Massano

Gerace²,

Borsari

et al. 2023

Drug Testing and Analysis

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Methoxpropamine (MXPr) is an arylcyclohexylamine dissociative drug structurally similar to 3-methoxyeticyclidine, ketamine, and deschloroketamine, recently appeared in the European illegal market, and was classified within the new psychoactive substances (NPS). Our study investigated the metabolism of MXPr to elucidate the distribution of the parent drug and its metabolites in body fluids and fur of 16 mice. After the intraperitoneal administration of MXPr (1, 3, and 10 mg/kg), urine samples from eight male and eight female mice were collected every hour for six consecutive hours and then at 12-to 24-h intervals. Additionally, plasma samples were collected 24 h after MXPr (1 and 3 mg/kg) administration. Urine and plasma were diluted 1:3 with acetonitrile/methanol (95:5) and directly injected into the UHPLC-QTOF-HRMS system. The phase-I and phase-II metabolites were preliminarily identified by means of the fragmentation patterns and the exact masses of both their precursor and fragment ions. Lastly, the mice fur was analyzed following an extraction procedure specific for the keratin matrix. Desmethyl-MXPr-glucoronide was identified in urine as the main metabolite, detected up to 24 h after administration. The presence of norMXPr in urine, plasma, and fur was also relevant, following a Ndealkylation process of the parent drug. Other metabolites that were identified in fur and plasma included desmethyl-MXPr and dihydro-MXPr. Knowledge of the MXPr metabolites evolution is likely to support their introduction as target compounds in NPS toxicological screening analysis on real samples, both to confirm intake and extend the detection window of the dissociative drug MXPr in the biological matrices.

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Section: Resultssupporting

confidence: 91%

“…Previous studies 21 identified CYP3A4 as the prevalent enzyme responsible for the N‐dealkylation of ketamine, with secondary role played also by CYP2B6 and CYP2C9. In analogy, CYP3A4 is likely to be responsible for the MXPr metabolism to its metabolite norMXPr.…”

Section: Resultsmentioning

confidence: 99%

Metabolic study of new psychoactive substance methoxpropamine in mice by UHPLC‐QTOF‐HRMS

Massano

Gerace²,

Borsari

et al. 2023

Drug Testing and Analysis

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“…The phase I metabolism of 3‐MeO‐PCE can be summarized as follows: On the methoxy‐substituted benzene ring, demethylation and hydroxylation occur (this was also reported to occur during the metabolism of MXE, 11 3‐MeO‐PCP, 3‐MeO‐PCPy, 13 and MXPr 35 ); hydroxylation occurs on the cyclohexyl group (this also occurred for 3‐MeO‐PCP and 3‐MeO‐PCPy 13 ); dealkylation reactions occur on aminoalkyl chains (this also occurred for ketamine, 36 DCK, MXE, 11 O‐PCE, 37 MXPr, 35 and 2F‐DCK). These metabolic reactions can also be observed in 3‐MeO‐PCE metabolic studies; however, some metabolic reactions were not observed in this experiment due to structural differences.…”

Section: Resultsmentioning

confidence: 98%

In vitro and in vivo metabolism of 3‐Methoxyeticyclidine in human liver microsomes, a zebrafish model, and two human urine samples based on liquid chromatography–high‐resolution mass spectrometry

Liu

Song

et al. 2023

Drug Testing and Analysis

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Abstract3‐Methoxyeticyclidine (3‐MeO‐PCE), a phencyclidine‐type substance, has a higher N‐methyl‐D‐aspartate receptor binding affinity than phencyclidine and an involvement in fatal intoxication cases. The aim of this study was to identify new biomarkers and biotransformation pathways for 3‐MeO‐PCE. In vitro models were established using zebrafish and human liver microsomes for analysis of the phases I and II metabolites of 3‐MeO‐PCE by liquid chromatography–high‐resolution mass spectrometry. Urine samples of known 3‐MeO‐PCE consumers in forensic cases were then subjected to analysis. Overall, 14 metabolites were identified in zebrafish and human liver microsomes, allowing postulation of the following metabolic pathways: hydroxylation, O‐demethylation, N‐dealkylation, dehydrogenation, combination, and glucuronidation or sulfation. 3‐MeO‐PCE and three metabolites (M2, M3, and M6) were detected in urine. We recommended M2 (the hydroxylation product) as a potential biomarker for documenting 3‐MeO‐PCE intake in clinical and forensic cases.

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“…So far, no metabolism data on 2-oxo-PCcP, 2-oxo-PCiP or 2-oxo-PCPr are available, nor have reports of their use in online forums, or seizures, been reported by relevant authorities. However, the 3-methoxy-analogs of 2-oxo-PCPr (MXPr) and 2-oxo-PCiP (MxiPr) have been reported as SPDs [28,29].…”

Section: Discussionmentioning

confidence: 99%

In Vivo and In Vitro Metabolic Fate and Urinary Detectability of Five Deschloroketamine Derivatives Studied by Means of Hyphenated Mass Spectrometry

Frankenfeld,

Wagmann,

Abelian

et al. 2024

Metabolites

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Ketamine derivatives such as deschloroketamine and deschloro-N-ethyl-ketamine show dissociative and psychoactive properties and their abuse as new psychoactive substances (NPSs) has been reported. Though some information is available on the biotransformation of dissociative NPSs, data on deschloro-N-cyclopropyl-ketamine deschloro-N-isopropyl-ketamine and deschloro-N-propyl-ketamine concerning their biotransformation and, thus, urinary detectability are not available. The aims of the presented work were to study the in vivo phase I and II metabolism; in vitro phase I metabolism, using pooled human liver microsomes (pHLMs); and detectability, within a standard urine screening approach (SUSA), of five deschloroketamine derivatives. Metabolism studies were conducted by collecting urine samples from male Wistar rats over a period of 24 h after their administration at 2 mg/kg body weight. The samples were analyzed using liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) and gas chromatography–mass spectrometry (GC-MS). The compounds were mainly metabolized by N-dealkylation, hydroxylation, multiple oxidations, and combinations of these metabolic reactions, as well as glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected. For the LC-HRMS/MS SUSA, compound-specific metabolites were identified, and suitable screening targets could be recommended and confirmed in pHLMs for all derivatives except for deschloro-N-cyclopropyl-ketamine. Using the GC-MS-based SUSA approach, only non-specific acetylated N-dealkylation metabolites could be detected.

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

Cited by 7 publications

References 24 publications

Metabolic study of new psychoactive substance methoxpropamine in mice by UHPLC‐QTOF‐HRMS

Metabolic study of new psychoactive substance methoxpropamine in mice by UHPLC‐QTOF‐HRMS

In vitro and in vivo metabolism of 3‐Methoxyeticyclidine in human liver microsomes, a zebrafish model, and two human urine samples based on liquid chromatography–high‐resolution mass spectrometry

In Vivo and In Vitro Metabolic Fate and Urinary Detectability of Five Deschloroketamine Derivatives Studied by Means of Hyphenated Mass Spectrometry

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