Determination of MDMA and its Metabolites in Blood and Urine by Gas Chromatography-Mass Spectrometry and Analysis of Enantiomers by Capillary Electrophoresis

Pizarro, Nieves; Ortuño, Jordi; Farré, Magı́; Hernández-López, Cándido; Pujadas, Mitona; Llebaría, Amadeu; Joglar, Jesús; Roset, Pere N.; Más, Marta; Segura, Jordi; Camı́, Jordi; Torre, Rafael de la

doi:10.1093/jat/26.3.157

Cited by 103 publications

(83 citation statements)

References 27 publications

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“…MDMA and MDA were dissolved in methanol for stock and working solutions for analysis. HHMA and HHA were synthesized as described previously (Ensslin et al, 1996;Pizarro et al, 2002) and prepared in methanol for stock dmd.aspetjournals.org and working solutions. Sodium metabisulfite (Sigma, St. Louis, MO) was dissolved in sterile water.…”

Section: Methodsmentioning

confidence: 99%

Ambient Temperature Effects on 3,4-Methylenedioxymethamphetamine-Induced Thermodysregulation and Pharmacokinetics in Male Monkeys

Banks¹,

Sprague²,

Kisor³

et al. 2007

Drug Metab Dispos

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ABSTRACT:Changes in ambient temperature are known to alter both the hyperthermic and the serotonergic consequences of 3,4-methylenedioxymethamphetamine (MDMA). Metabolism of MDMA has been suggested to be a requisite for these neurotoxic effects, whereas the hyperthermic response is an important contributing variable. The aim of the present study was to investigate the interaction between ambient temperature, MDMA-induced thermodysregulation, and its metabolic disposition in monkeys. MDMA (1.5 mg/kg i.v.) was administered noncontingently at cool (18°C; n ‫؍‬ 5), room (24°C; n ‫؍‬ 7), and warm (31°C; n ‫؍‬ 7) ambient temperatures. For 240 min following MDMA administration, core temperature was recorded and blood samples were collected for analysis of MDMA and its metabolites 3,4-dihydroxymethamphetamine (HHMA), 3,4-dihydroxyamphetamine, and 3,4-methylenedioxyamphetamine (MDA). A dose of 1.5 mg/kg MDMA induced a hypothermic response at 18°C, a hyperthermic response at 31°C, and did not significantly change core temperature at 24°C. Regardless of ambient temperature, plasma MDMA concentrations reached maximum within 5 min, and HHMA was a major metabolite. Curiously, the approximate elimination half-life (t 1/2 ) of MDMA at 18°C (136 min) and 31°C (144 min) was increased compared with 24°C (90 min) and is most likely because of volume of distribution changes induced by core temperature alterations. At 18°C, there was a significantly higher MDA area under the concentration-time curve (AUC) and a trend for a lower HHMA AUC compared with 24°C and 31°C, suggesting that MDMA disposition was altered. Overall, induction of hypothermia in a cool environment by MDMA may alter its disposition. These results could have implications for MDMA-induced serotonergic consequences.

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Section: Methodsmentioning

confidence: 99%

Ambient Temperature Effects on 3,4-Methylenedioxymethamphetamine-Induced Thermodysregulation and Pharmacokinetics in Male Monkeys

Banks¹,

Sprague²,

Kisor³

et al. 2007

Drug Metab Dispos

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“…Mephedrone-D3 was used as internal standard. MDMA concentrations in plasma were measured by GC/MS (Pizarro et al, 2002). Human pharmacology of mephedrone E Papaseit et al…”

Section: Pharmacokineticsmentioning

confidence: 99%

Human Pharmacology of Mephedrone in Comparison with MDMA

Papaseit

Pérez‐Mañá

Mateus

et al. 2016

Neuropsychopharmacol

132

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Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-methylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone and its relative abuse liability compared with MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in ClinicalTrials.gov (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentration values for mephedrone and MDMA peaked at 1.25 h and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 h and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by the users.

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“…We showed that the catechol-metabolites that significantly reduced THLE cell viability were also responsible for the reduction of GSH, which was in line with results from other studies (Carvalho et al 2002; To verify these findings in a model where metabolism can occur, we used primary rat hepatocytes. However, catechol-metabolites are the main metabolites formed in humans (Segura et al 2001;Pizarro et al 2002;, while in rats the main MDMA-metabolite is the non-cytotoxic MDA (Cho et al 1990;Lin et al 1992). Indeed, the levels of GSH and cell viability were not significantly decreased in primary rat hepatocytes upon MDMA exposure.…”

Section: Phase II Metabolismmentioning

confidence: 99%

A mechanistic insight into 3,4-methylenedioxymethamphetamine (“ecstasy”)-mediated hepatotoxicity

Antolino-Lobo

Meulenbelt

Berg

et al. 2011

Veterinary Quarterly

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3,4-Methylenedioxymethamphetamine (MDMA, ''ecstasy'') is a popular drug of abuse among young people with stimulant and hallucinogenic properties. The drug is generally thought to be safe among consumers due to its low-mortality rates. However, MDMA-adverse effects can occur and the risks are not clearly associated to a specific pattern since the consumption quantity seems not to be correlated with the initiation and severity of the injury. MDMA-mediated adverse health effects have been widely studied and can be evoked by multiple factors such as hyperthermia, polydrug abuse (drug-drug interactions), the altered release of neurotransmitters, impairment of mitochondrial function and apoptosis, metabolism and immune responses. Another adverse effect often associated with MDMA is liver toxicity, yet the mechanism of MDMA-induced liver toxicity is not completely understood. A critical starting point appears to be the hepatic metabolism of MDMA by phase I and II enzymes, leading to reactive metabolites. Elucidating the mechanism of hepatic injury mediated by MDMA is of high toxicological and clinical relevance. In this review, an overview of the literature and the latest findings with respect to the mechanism of MDMA-mediated liver toxicity is described.

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Determination of MDMA and its Metabolites in Blood and Urine by Gas Chromatography-Mass Spectrometry and Analysis of Enantiomers by Capillary Electrophoresis

Cited by 103 publications

References 27 publications

Ambient Temperature Effects on 3,4-Methylenedioxymethamphetamine-Induced Thermodysregulation and Pharmacokinetics in Male Monkeys

Ambient Temperature Effects on 3,4-Methylenedioxymethamphetamine-Induced Thermodysregulation and Pharmacokinetics in Male Monkeys

Human Pharmacology of Mephedrone in Comparison with MDMA

A mechanistic insight into 3,4-methylenedioxymethamphetamine (“ecstasy”)-mediated hepatotoxicity

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