Determination of a new designer drug, N-hydroxy-3,4-methylenedioxymethamphetamine and its metabolites in rats using ultra-performance liquid chromatography–tandem mass spectrometry

Kikura‐Hanajiri, Ruri; Kawamura, Maiko; Miyajima, Atsuko; Sunouchi, Momoko; Goda, Yukihiro

doi:10.1016/j.forsciint.2010.02.013

Cited by 18 publications

(9 citation statements)

References 16 publications

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“…The finding (ii) was in accordance with the result of the direct analysis of the N-OH-MDMA-glucuronide. The findings (iii) and (iv) were consistent with the previous works (Kamata et al, 2010;Kikura-Hanajiri et al, 2010).…”

Section: Urinary Excretion Profiles After Oral N-oh-mdma Administratisupporting

confidence: 92%

“…In vitro metabolic studies using human liver S9 fraction (Kamata et al, 2010) or human hepatocytes showed N-OH-MDMA was mainly metabolised to MDMA and 3, 4-methylenedioxyamphetamine (MDA, Figure 1C). In in vivo studies, MDMA and MDA were the main urinary metabolites of intraperitoneally administered N-OH-MDMA in rats, and only very small amounts were excreted as the unchanged form and the demethylated form N-hydroxy-3,4-MDA (N-OH-MDA, Figure 1D) (Kamata et al, 2010;Kikura-Hanajiri et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Urinary excretion profiles ofN-hydroxy-3,4-methylenedioxymethamphetamine in rats

et al. 2011

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N-hydroxy-3,4-methylenedioxymethamphetamine (N-OH-MDMA) is a psychedelic illicit drug that has recently been circulating in Japan. The aims of this study were (i) to optimise enzymatic hydrolysis conditions of the conjugated forms of N-OH-MDMA and its demethylated metabolite N-hydroxy-3,4-methylenedioxyamphetamine (N-OH-MDA), (ii) to investigate the urinary excretion profiles of N-OH-MDMA in rats, and (iii) to compare urinary excretion profiles of N-OH-MDMA and 3,4-methylenedioxymethamphetamine (MDMA). Conjugated forms of the N-hydroxylated compounds (N-OH-MDMA and N-OH-MDA) were almost successfully hydrolysed to their nonconjugated forms under anaerobic conditions after helium purging of the solution. The sum of N-OH-MDMA and N-OH-MDA was used to evaluate the amount of excreted N-hydroxylated metabolites because of degradation of N-OH-MDMA to N-OH-MDA during hydrolysis. Up to 24 h after oral administration of N-OH-MDMA oxalate, the main urinary metabolites were MDMA (14.3% of dose) and 3,4-MDA (7.7% of dose). Most of the N-hydroxylated forms were excreted as glucuronide conjugates. The total amount of N-hydroxylated metabolites after hydrolysis was 1.1% of dose. Urinary excretion profiles of MDMA were similar to that of N-OH-MDMA. It may be difficult to differentiate between abuse of MDMA and N-OH-MDMA by urine analysis.

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Section: Urinary Excretion Profiles After Oral N-oh-mdma Administratisupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Urinary excretion profiles ofN-hydroxy-3,4-methylenedioxymethamphetamine in rats

et al. 2011

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“…Although the polymorphisms of enzymes and the differences of species can affect some metabolic patterns, it is important for public health and forensic toxicology to inform potential toxicity by the interaction between compounds with similar chemical structures. There are various designer drugs including phenethylamine derivatives such as N ‐hydroxy MDMA and methylone that are synthesized in clandestine laboratories and are available on the street (36,37). These designer drugs as well as MDMA and MA may alter the pharmacokinetics with each other.…”

Section: Resultsmentioning

confidence: 99%

Interaction of 3,4‐Methylenedioxymethamphetamine and Methamphetamine During Metabolism byIn VitroHuman Metabolic Enzymes and in Rats*

Kuwayama

Tsujikawa

Miyaguchi

et al. 2011

Journal of Forensic Sciences

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Illicit amphetamine-type stimulant (ATS) tablets commonly contain one or more active ingredients, which have hallucinogenic and/or stimulant effects. Because components such as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MA) in ATS tablets have similar chemical structures, they could be metabolized by common metabolic enzymes. To investigate potential metabolic interactions of ATS tablet components, we studied the in vitro metabolism of MDMA and MA using human metabolic enzymes. MDMA and MA were mainly metabolized by cytochrome P450 2D6 (CYP2D6) and mutually inhibited the production of their main metabolites. In vivo experiments were also performed using intravenous administration of MDMA, MA, or their mixture to rats. The plasma concentrations of MDMA and MA after co-administration were higher than those after administration of MDMA or MA alone. The results in this study imply that multiple components in ATS tablets can interact to mutually inhibit their metabolism and potentially enhance the toxicity of each component.

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“…These common fragments are likely to be found for all structurally related compounds. For example, the same fragmentation patterns were found for OH‐derivatives of MDMA and MDA that have also been sold as new designer drugs in some drug markets; the fragment ion at m / z 135 was found in the fragmentation pattern of N ‐methyl‐1‐(3,4‐methylenedioxyphenyl)‐2‐butanamine, a relatively novel amphetamine‐type substance.…”

Section: Resultsmentioning

confidence: 59%

Screening of methylenedioxyamphetamine‐ and piperazine‐derived designer drugs in urine by LC–MS/MS using neutral loss and precursor ion scan

et al. 2013

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This study describes a method for the screening of methylenedioxyamphetamine- and piperazine-derived compounds in urine by liquid chromatography-tandem mass spectrometry. These substances, characterized by possessing common moieties, are screened using precursor ion and neutral loss scan mode and then quantified in multiple reaction monitoring acquisition mode. Based on the product-ion spectra of different known molecules, chosen as 'model', characteristic neutral losses and product ions were selected: piperazines were detected in precursor ion scan of m/z 44 and neutral loss of 43 and 86 while amphetamines in precursor ion scan of m/z 133, 135 and 163. The applicability of the screening approach was studied in blank urine spiked with selected analytes and processed by solid-phase extraction. Linearity, matrix effect, precision, accuracy, limits of detection and limits of quantification were evaluated both for the screening and the quantification methods. The ability of the screening method to provide semi-quantitative data was demonstrated. This method appears to be a useful tool for the identification of designer drugs derived from piperazines or methylenedioxyamphetamines and can be potentially applied to other drug classes.

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Determination of a new designer drug, N-hydroxy-3,4-methylenedioxymethamphetamine and its metabolites in rats using ultra-performance liquid chromatography–tandem mass spectrometry

Cited by 18 publications

References 16 publications

Urinary excretion profiles ofN-hydroxy-3,4-methylenedioxymethamphetamine in rats

Urinary excretion profiles ofN-hydroxy-3,4-methylenedioxymethamphetamine in rats

Interaction of 3,4‐Methylenedioxymethamphetamine and Methamphetamine During Metabolism byIn VitroHuman Metabolic Enzymes and in Rats*

Screening of methylenedioxyamphetamine‐ and piperazine‐derived designer drugs in urine by LC–MS/MS using neutral loss and precursor ion scan

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