Ketamine-derived designer drug methoxetamine: metabolism including isoenzyme kinetics and toxicological detectability using GC-MS and LC-(HR-)MSn

@article{Meyer2013KetaminederivedDD,
  title={Ketamine-derived designer drug methoxetamine: metabolism including isoenzyme kinetics and toxicological detectability using GC-MS and LC-(HR-)MSn},
  author={M. Meyer and M. Bach and J. Welter and M. Bovens and A. Turcant and H. Maurer},
  journal={Analytical and Bioanalytical Chemistry},
  year={2013},
  volume={405},
  pages={6307-6321}
}
Methoxetamine (MXE; 2-(3-methoxyphenyl)-2-(N-ethylamino)-cyclohexanone), a ketamine analog, is a new designer drug and synthesized for its longer lasting and favorable pharmacological effects over ketamine. The aims of the presented study were to identify the phases I and II metabolites of MXE in rat and human urine by GC-MS and LC-high-resolution (HR)-MSn and to evaluate their detectability by GC-MS and LC-MSn using authors’ standard urine screening approaches (SUSAs). Furthermore, human… Expand
A study of in vitro metabolism and cytotoxicity of mephedrone and methoxetamine in human and pig liver models using GC/MS and LC/MS analyses
Abstract In the current study, the metabolism of two novel psychoactive substances (NPSs), mephedrone and methoxetamine (MXE), was studied in vitro in pig liver microsomes to determine potentialExpand
GC-MS and LC-(high-resolution)-MSn studies on the metabolic fate and detectability of camfetamine in rat urine
TLDR
The metabolic fate and the detectability of CFA in urine was studied and to elucidate which cytochrome-P450 (CYP) isoenzymes are involved in the main metabolic steps, with the hydroxy-aryl CFA and the corresponding glucuronide being the most abundant. Expand
Toxicokinetics of novel psychoactive substances: characterization of N-acetyltransferase (NAT) isoenzymes involved in the phase II metabolism of 2C designer drugs.
TLDR
The aim of this study was to elucidate the role of the recombinant human N-acetyltransferase (NAT) isoforms 1 and 2 in the phase II metabolism of 2Cs and show NAT2 could be the only isoform catalyzing the reaction in vitro, hence it should be theonly relevant enzyme for in vivo acetylation. Expand
Synthesis and identification of deschloroketamine metabolites in rats' urine and a quantification method for deschloroketamine and metabolites in rats' serum and brain tissue using liquid chromatography tandem mass spectrometry.
TLDR
A metabolomics study for deschloroketamine via non-targeted screening of urine samples employing liquid chromatography combined with high-resolution mass spectrometry and developed and validated a multiple reaction monitoring method using a triple quadrupole instrument to track metabolites of deschlorketamine. Expand
Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue—Behavioural, pharmacokinetic and metabolic studies in the Wistar rat
Methoxetamine (MXE) is a novel psychoactive compound (NPS) that emerged in 2010 as a substitute for the dissociative anaesthetic ketamine. MXE has a reputation of carrying a lower risk of harm thanExpand
Studies on the metabolism and the detectability of 4-methyl-amphetamine and its isomers 2-methyl-amphetamine and 3-methyl-amphetamine in rat urine using GC-MS and LC-(high-resolution)-MSn
TLDR
The aims of the presented work were to study the metabolism and detectability of each isomer in urine samples of 4-MA and its isomers and to confirm the intake of a commonly used dose of the MAs with an additional workup in rat urine. Expand
oxicokinetics of novel psychoactive substances : Characterization of-acetyltransferase ( NAT ) isoenzymes involved in the phase II etabolism of 2 C designer drugs
The 2,5-dimethoxyphenethylamine-derived designer drugs (so-called “2Cs”) recently became of great importance on the illicit drug market as stimulating hallucinogens. They are distributed and consumedExpand
Synthesis of methoxetamine, its metabolites and deuterium labelled analog as analytical standards and their HPLC and chiral capillary electrophoresis separation
Methoxetamine, a designer drug marketed as a replacement for the dissociative anaesthetic ketamine, has been associated with significant numbers of hospital related intoxications and deaths inExpand
What is the contribution of human FMO3 in the N-oxygenation of selected therapeutic drugs and drugs of abuse?
TLDR
The successful application of a modified RAF approach including F MO3 proved the importance of FMO3 in the N-oxygenation of DOAs in human metabolism. Expand
Fatal Intoxication with Methoxetamine
TLDR
The high concentration of MXE in blood and urine and the circumstances of the case indicate an unintentional, fatal intoxication with this substance. Expand
...
1
2
3
4
...

References

SHOWING 1-10 OF 34 REFERENCES
2-Methiopropamine, a thiophene analogue of methamphetamine: studies on its metabolism and detectability in the rat and human using GC-MS and LC-(HR)-MS techniques
TLDR
Following the administration of a typical user’s dose, 2-MPA and its metabolites were identified in rat urine using the authors’ GC-MS and the LC-MSn screening approaches and the following major metabolic pathways were proposed: N-demethylation, hydroxylation at the side chain and at the thiophene ring, and combination of these transformations followed by glucuronidation and/or sulfation. Expand
New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS and their detectability in urine.
TLDR
For both compounds, detection in rat urine was possible within the authors' systematic toxicological analysis using both GC-MS and LC-MS(n) after a suspected recreational users dose. Expand
Metabolism and toxicological detection of the designer drug 4-chloro-2,5-dimethoxyamphetamine in rat urine using gas chromatography-mass spectrometry
TLDR
The authors’ systematic toxicological analysis procedure using full-scan gas chromatography-mass spectrometry after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of an intake of a dose of DOC in rat urine that corresponds to a common drug user’s dose. Expand
Development of the first metabolite-based LC-MSn urine drug screening procedure-exemplified for antidepressants
TLDR
The presentedLC-MSn method complements established GC-MS or LC-MS procedures in the authors’ lab and allowed detecting unknown compounds based on known fragment structures and confirms the body passage. Expand
Drugs of abuse screening in urine as part of a metabolite-based LC-MSn screening concept
TLDR
The presented LC-MSn method complements the well-established gas chromatography-mass spectroscopy procedure in the authors’ laboratory and could be used for drug screening in clinical and forensic toxicology and in doping control. Expand
Investigation on the Enantioselectivity of the Sulfation of the Methylenedioxymethamphetamine Metabolites 3,4-Dihydroxymethamphetamine and 4-Hydroxy-3-Methoxymethamphetamine using the Substrate-Depletion Approach
Different pharmacokinetic properties are known for the two enantiomers of the entactogen 3,4-methylendioxy-methamphetamine (MDMA), most likely due to enantioselective metabolism. The aim of theExpand
Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine
TLDR
These three analytically confirmed cases demonstrate that acute methoxetamine-related toxicity is associated with both “dissociative” and “sympathomimetic” clinical features, and is useful to clinical pharmacologists, not only in managing individuals with acute methxetamine toxicity but also in advising the appropriate legislative authorities on the risk of acute harm related to methoxETamine use. Expand
Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites: Part 3 mass spectra (m/z222 to 777 amu).
Volume 1 (Methods, Tables). Methods. 1 Introduction. 2 Experimental Section. 2.1 Origin and choice of samples. 2.2 Sample preparation. 2.2.1 Standard extraction procedures. 2.2.1.1 StandardExpand
Ketamine-like effects after recreational use of methoxetamine.
TLDR
The first case of analytically confirmed intravenous methoxetamine abuse in a 19-year-old man is reported, with signs and symptoms consistent with ketamine-induced adverse effects and resolved with symptomatic treatment. Expand
Analysis of anonymous pooled urine from portable urinals in central London confirms the significant use of novel psychoactive substances.
TLDR
Analysis of pooled urine samples collected anonymously from stand-alone urinals in a large inner city can detect the use of recreational drugs, NPS and anabolic steroids and indicates actual drug use, metabolism and elimination rather than simply discarded drugs in the urinals. Expand
...
1
2
3
4
...