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Sample records for 3,4-methylenedioxyamphetamine

  1. The pharmacokinetics and liver metabolism of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) in rats.

    Ravis, W R; Valaer, A K; Brzozowski, D; Clark, C R

    1994-01-01

    The metabolism and disposition of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) was studied by utilizing rat liver slices as well as by intravenous pharmacokinetic studies in rats. In the liver slice experiments, N-OH MDA (16 micrograms/ml) was incubated with rat liver slices and the disappearance of N-OH MDA and the appearance of MDA were observed over 2 hours. Drug and metabolites were assayed by a reverse phase high performance liquid chromatographic procedure including a C8 column and UV detection. N-OH MDA disappeared from the plasma at an apparent first-order rate with a t1/2 of 36.3 +/- 8.4 min. By the end of 2 hours, approximately 85% of the N-OH MDA was biotransformed to MDA. Following placement of jugular cannulas in rats, a dose of 15 mg/kg of N-OH MDA was administered intravenously. With rapid blood sampling, a t1/2 of 0.86 +/- 0.12 min was observed for N-OH MDA. A total body clearance of 9.09 +/- 2.06 L/hr/kg and a volume of distribution of 0.184 +/- 0.022 L/kg were noted. Plasma concentrations of MDA were observed after the N-OH MDA dose to rats. The MDA t1/2 after N-OH MDA dosing was 1.68 +/- 0.29 hours with peak plasma concentrations at 8 min. No other major metabolites could be detected in liver slice, plasma, or urine samples. Both sets of studies demonstrate the rapid conversion of N-OH MDA to MDA in rats. PMID:8208060

  2. N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration

    Ninković Milica

    2004-01-01

    Full Text Available Background. The underlying mechanisms of N-Methyl-3,4-methylenedioxyamphetamine-MDMA-induced hepatotoxicity are still unknown. The aim of this study was to evaluate hepatic oxido-reductive status in the rats liver after the single and repeated administration of MDMA. Methods. MDMA was dissolved in distilled water and administered in the doses of 5 mg, 10 mg, 20 mg, and 40 mg/kg. The animals from the acute experiment were treated per os with the single dose of the appropriate solution, through the orogastric tube. The animals from the chronic experiment were treated per os, with the doses of 5, 10, or 20 mg/kg of MDMA every day during 14 days. The control groups were treated with water only. Eight hours after the last dose, the animals were sacrificed, dissected their livers were rapidly removed, frozen and stored at -70°C until the moment of analysis. The parameters of oxidative stress in the crude mitochondrial fractions of the livers were analyzed. Results. Superoxide dismutase (SOD activity increased in the livers of the animals that were treated with single doses of MDMA. Chronically treated animals showed the increased SOD activity only after the highest dose (20 mg/kg. The content of reduced glutathione decreased in both groups, but the depletion was much more expressed after the single administration. Lipid peroxidation index increased in dose-dependent manner in both groups, being much higher after the single administration. Conclusion. The increased index of lipid peroxidation and the decreased reduced glutathione levels suggested that MDMA application induced the state of oxidative stress in the liver. These changes were much more expressed after the single administration of MDMA.

  3. Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection

    Nakamoto, Akihiro [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nishida, Manami [Hiroshima University Technical Center, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Saito, Takeshi [Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa 259-1143 (Japan); Kishiyama, Izumi; Miyazaki, Shota [GL Sciences Inc., Sayamagahara 237-2, Iruma, Saitama 358-0032 (Japan); Murakami, Katsunori [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nagao, Masataka [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Namura, Akira, E-mail: namera@hiroshima-u.ac.jp [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan)

    2010-02-19

    A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d{sub 5} was used as an internal standard. The linear ranges were 0.01-5.0 {mu}g mL{sup -1} for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 {mu}g mL{sup -1} for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation {>=}0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 {mu}g mL{sup -1} of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio {>=} 3) in urine was 5 ng mL{sup -1} for MA and MDMA and 10 ng mL{sup -1} for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation.

  4. Quantitative Silylation Speciations of Primary Phenylalkyl Amines, Including Amphetamine and 3,4-Methylenedioxyamphetamine Prior to Their Analysis by GC/MS.

    Molnár, Borbála; Fodor, Blanka; Boldizsár, Imre; Molnár-Perl, Ibolya

    2015-10-20

    A novel, quantitative trimethylsilylation approach derivatizing 11 primary phenylalkyl amines (PPAAs), including amphetamine (A) and 3,4-methylenedioxyamphetamine (MDA), was noted. Triggering the fully derivatized ditrimethylsilyl (diTMS) species with the N-methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA) reagent, a new principle was recognized followed by GC/MS. In the course of method optimization, the complementary impact of solvents (acetonitrile, ACN; ethyl acetate, ETAC; pyridine, PYR) and catalysts (trimethylchlorosilane, TMCS; trimethyliodosilane, TMIS) was studied: the role of solvent and catalyst proved to be equally crucial. Optimum, proportional, huge responses were obtained with the MSTFA/PYR = 2/1-9/1 (v/v) reagent applying catalysts; A and MDA needed the TMIS, while the rest of PPAAs provided the diTMS products also with TMCS. Similar to derivatives generated with hexamethyldisilazane and perfluorocarboxylic acid (HMDS and PFCA) ( Molnár et al. Anal. Chem. 2015 , 87 , 848 - 852 ), the fully silylated PPAAs offer several advantages. Both of our methods save time and cost by allowing for direct injection of analytes into the column; this is in stark contrast with the requirement to evaporate acid anhydrides by nitrogen prior to their injection. Efficiences of the novel catalyzed trimethylsilylation (MSTFA) and our recently introduced (now, for A and MDA extended) acylation principle were contrasted. Catalyzed trimethylsilylation led to diTMS derivatives resulting in on average a 1.7 times larger response compared to the corresponding acylated species. Catalyzed trimethylsilylation of PPAAs, A, and MDA were characterized with retention, mass fragmentation, and analytical performance properties (R(2), LOQ values). The practical utility of ditrimethylsilyation was shown by analyzing A in urine and mescaline (MSC) in cactus samples. PMID:26412806

  5. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine

    McKenna, D.J.; Guan, X.M.; Shulgin, A.T. (Department of Neurology Neurological Sciences, Stanford University Medical Center, CA (USA))

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.

  6. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine.

    McKenna, D J; Guan, X M; Shulgin, A T

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives (+/-)fenfluramine, (+/-)norfenfluramine, (+/-)MDE, (+/-)PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners. PMID:1829838

  7. 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites

    This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%) in the density of [3H]paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of [3H]mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals

  8. 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of (/sup 3/H)paroxetine-labeled serotonin uptake sites

    Battaglia, G.; Yeh, S.Y.; O' Hearn, E.; Molliver, M.E.; Kuhar, M.J.; De Souza, E.B.

    1987-09-01

    This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%) in the density of (/sup 3/H)paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of (/sup 3/H)mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.

  9. 3,4-methylenedioxyamphetamine upregulates p75 neurotrophin receptor protein expression in the rat brain.

    Wang, Chaomin; Peng, Zugui; Kuang, Weihong; Zheng, Hanyu; Long, Jiang; Wang, Xue

    2012-04-25

    The p75 neurotrophin receptor, which is a member of the tumor necrosis factor receptor superfamily, facilitates apoptosis during development and following central nervous system injury. Previous studies have shown that programmed cell death is likely involved in the neurotoxic effects of 3, 4-methylenedioxy-N-methylamphetamine (MDMA), because MDMA induces apoptosis of immortalized neurons through regulation of proteins belonging to the Bcl-2 family. In the present study, intraperitoneal injection of different doses of MDMA (20, 50, and 100 mg/kg) induced significant behavioral changes, such as increased excitability, increased activity, and irritability in rats. Moreover, changes exhibited dose-dependent adaptation. Following MDMA injection in rat brain tissue, the number of apoptotic cells dose-dependently increased and p75 neurotrophin receptor expression significantly increased in the prefrontal cortex, cerebellum, and hippocampus. These findings confirmed that MDMA induced neuronal apoptosis, and results suggested that this effect was related by upregulated protein expression of the p75 neurotrophin receptor. PMID:25722682

  10. 3,4-methylenedioxyamphetamine upregulates p75 neurotrophin receptor protein expression in the rat brain

    Chaomin Wang; Zugui Peng; Weihong Kuang; Hanyu Zheng; Jiang Long; Xue Wang

    2012-01-01

    The p75 neurotrophin receptor, which is a member of the tumor necrosis factor receptor superfamily, facilitates apoptosis during development and following central nervous system injury. Previous stu-dies have shown that programmed cell death is likely involved in the neurotoxic effects of 3, 4-methylenedioxy-N-methylamphetamine (MDMA), because MDMA induces apoptosis of immor-talized neurons through regulation of proteins belonging to the Bcl-2 family. In the present study, intraperitoneal injection of different doses of MDMA (20, 50, and 100 mg/kg) induced significant behavioral changes, such as increased excitability, increased activity, and irritability in rats. Moreover, changes exhibited dose-dependent adaptation. Following MDMA injection in rat brain tissue, the number of apoptotic cells dose-dependently increased and p75 neurotrophin receptor expression significantly increased in the prefrontal cortex, cerebellum, and hippocampus. These findings confirmed that MDMA induced neuronal apoptosis, and results suggested that this effect was related by upregulated protein expression of the p75 neurotrophin receptor.

  11. MDMA (N-methyl-3,4-methylenedioxyamphetamine) and its Stereoisomers: Similarities and Differences in Behavioral Effects in an Automated Activity Apparatus in Mice

    Young, Richard; Glennon, Richard A.

    2007-01-01

    Racemic MDMA (0.3 – 30 mg/kg), S(+)-MDMA (0.3 – 30 mg/kg), R(-)-MDMA (0.3 – 50 mg/kg) and saline vehicle (10 ml/kg) were comprehensively evaluated in fully automated and computer-integrated activity chambers, which were designed for mice, and provided a detailed analysis of the frequency, location, and/or duration of 18 different activities. The results indicated that MDMA and its isomers produced stimulation of motor actions, with S(+)-MDMA and (±)-MDMA usually being more potent than R(-)-MD...

  12. Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA)

    The use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has increased in recent years; it can lead to life-threatening hyperthermia and serotonin syndrome. Human and rodent males appear to be more sensitive to acute toxicity than are females. MDMA is metabolized to five main metabolites by the enzymes CYP1A2, CYP2D and COMT. Little is presently known about sex-dependent differences in the pharmacokinetics of MDMA and its metabolites. We therefore analyzed MDMA disposition in male and female rats by measuring the plasma and urine concentrations of MDMA and its metabolites using a validated LC-MS method. MDA AUClast and Cmax were 1.6- to 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA Cmax and AUClast were 3.2- and 3.5-fold higher, respectively. MDMA renal clearance was 1.26-fold higher in males, and that of MDA was 2.2-fold higher. MDMA AUClast and t1/2 were 50% higher in females given MDMA (1 mg/kg iv). MDA Cmax and AUClast were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUClast of MDA was 0.73-fold lower in males given 1 mg/kg iv MDA. The volumes of distribution of MDMA and MDA at steady-state were similar in the two sexes. These data strongly suggest that differences in the N-demethylation of MDMA to MDA are major influences on the MDMA and MDA pharmacokinetics in male and female rats. Hence, males are exposed to significantly more toxic MDA, which could explain previously reported sexual dysmorphism in the acute effects and toxicity of MDMA in rats.

  13. Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenylalkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

    Takeshi Kumazawa; Kenji Hara; Chika Hasegawa; Seisaku Uchigasaki; Xiao-Pen Lee; Hiroshi Seno; Osamu Suzuki; Keizo Sato

    2011-01-01

    Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenylalkylamine designer drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), 3,4-methylenedioxyamphetamine (MDA), and 3,4-(methylenedioxyphenyl)-2-butanamine (BDB), are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA) anhydride and analyzed by gas chromatography/mass sp...

  14. Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice

    Kuteykin-Teplyakov, Konstantin; Maldonado, Rafael

    2014-01-01

    Social behavior plays a fundamental role in life of many animal species, allowing the interaction between individuals and sharing of experiences, needs, and goals across them. In humans, some neuropsychiatric diseases, including anxiety, posttraumatic stress disorder and autism spectrum disorders, are often characterized by impaired sociability. Here we report that N-Methyl-3,4-methylenedioxyamphetamine (MDMA, "Ecstasy") at low dose (3mg/kg) has differential effects on mouse social behavior. ...

  15. Evaluation of drug incorporation into hair segments and nails by enantiomeric analysis following controlled single MDMA intakes

    Madry, Milena M; Steuer, Andrea E.; Hysek, Cédric M.; Liechti, Matthias E; Baumgartner, Markus R.; Kraemer, Thomas

    2016-01-01

    Incorporation rates of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) into hair and nails were investigated after controlled administration. Fifteen subjects without MDMA use received two doses of 125 mg of MDMA. Hair, nail scrapings, and nail clippings were collected 9-77 days after the last administration (median 20 days). Hair samples were analyzed in segments of 1- to 2-cm length. After chiral derivatization with N-(2,4-d...

  16. 1-phenylethylamines: a new series of illicit drugs?

    King, L A; Poortman-van der Meer, A J; Huizer, H

    1996-02-01

    Since 1993 many seizures of 1-phenylethylamine have been made in several European countries. It was originally thought that 1-phenylethylamine had been made in error, but later information suggested that it had been prepared deliberately. The related compounds, 1-amino-1-(4-methylphenyl)ethane and 1-methylamino-1-phenylethane and the 1-propanamine isomer of 3,4-methylenedioxyamphetamine, have also occurred in isolated cases. Analytical data are presented on these amines as well as a number of Leuckart impurities in 1-phenylethylamine. The pharmacological effects of these substances are largely unknown. PMID:8819989

  17. Selenoprotein W was Correlated with the Protective Effect of Selenium on Chicken Myocardial Cells from Oxidative Damage.

    Liu, Wei; Yao, Haidong; Zhao, Wenchao; Shi, Yuguang; Zhang, Ziwei; Xu, Shiwen

    2016-06-01

    Selenium (Se) mainly performs its function through Se-containing proteins. Selenoprotein W (SelW), one member of the selenoprotein family, plays important roles in the normal function of the heart. To investigate the possible relationship between Se and SelW for the regulation of oxidative damage in chicken embryo myocardial cells, we treated myocardial cells with Se and H2O2. Then, the levels of lactate dehydrogenase (LDH) and 3,4-methylenedioxyamphetamine in the culture media, levels of SelW, inflammatory genes NF-κB, tumor necrosis factor (TNF)-α, p53, and the cell cycle were analyzed. Furthermore, the correlation between SelW and the levels of these factors was determined. The results indicated that Se treatment increased the expression of SelW (P chicken myocardial cells. PMID:26463750

  18. The synthesis, mass spectrometric properties and identification of some N,N-di-(β-arylisopropyl)formamides related to the synthesis of ring-modified amphetamines.

    Błachut, Dariusz; Danikiewicz, Witold; Wojtasiewicz, Krystyna; Olejnik, Marian; Kalinowska, Iwona; Szawkało, Joanna; Czarnocki, Zbigniew

    2011-03-20

    This study examines the electron impact (EI) induced mass spectrometric behavior of several N,N-di-(β-arylisopropyl)formamides, which are connected to the Leuckart synthesis of some amphetamine analogues. Emphasis is laid on the fragmentation paths, which are common for all compounds under investigation and may be used in construction of the prediction scheme useful for identification of similar impurities, especially in absence of desirable authentic material. On the basis of this scheme several new N,N-di-(β-arylisopropyl)formamides have been identified in selected amphetamine analogues synthesized by the Leuckart method, including 4-methylthioamphetamine (4-MTA), 4-fluoroamphetamine (4-FA), 4-methylamphetamine, 3-trifluoromethylamphetamine, 3,4-methylenedioxyamphetamine (MDA), 2,5-dimethoxyamphetamine (2,5-DMA), 2,4,5- and 3,4,5-trimethoxyamphetamines (2-TMA and 3-TMA). PMID:20846801

  19. Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2).

    Tournier, Nicolas; Chevillard, Lucie; Megarbane, Bruno; Pirnay, Stéphane; Scherrmann, Jean-Michel; Declèves, Xavier

    2010-08-01

    Drug interaction with P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may influence its tissue disposition including blood-brain barrier transport and result in potent drug-drug interactions. The limited data obtained using in-vitro models indicate that methadone, buprenorphine, and cannabinoids may interact with human P-gp; but almost nothing is known about drugs of abuse and BCRP. We used in vitro P-gp and BCRP inhibition flow cytometric assays with hMDR1- and hBCRP-transfected HEK293 cells to test 14 compounds or metabolites frequently involved in addiction, including buprenorphine, norbuprenorphine, methadone, ibogaine, cocaine, cocaethylene, amphetamine, N-methyl-3,4-methylenedioxyamphetamine, 3,4-methylenedioxyamphetamine, nicotine, ketamine, Delta9-tetrahydrocannabinol (THC), naloxone, and morphine. Drugs that in vitro inhibited P-gp or BCRP were tested in hMDR1- and hBCRP-MDCKII bidirectional transport studies. Human P-gp was significantly inhibited in a concentration-dependent manner by norbuprenorphine>buprenorphine>methadone>ibogaine and THC. Similarly, BCRP was inhibited by buprenorphine>norbuprenorphine>ibogaine and THC. None of the other tested compounds inhibited either transporter, even at high concentration (100 microm). Norbuprenorphine (transport efflux ratio approoximately 11) and methadone (transport efflux ratio approoximately 1.9) transport was P-gp-mediated; however, with no significant stereo-selectivity regarding methadone enantiomers. BCRP did not transport any of the tested compounds. However, the clinical significance of the interaction of norbuprenorphine with P-gp remains to be evaluated. PMID:19887017

  20. Duloxetine inhibits effects of MDMA ("ecstasy" in vitro and in humans in a randomized placebo-controlled laboratory study.

    Cédric M Hysek

    Full Text Available UNLABELLED: This study assessed the effects of the serotonin (5-HT and norepinephrine (NE transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence. TRIAL REGISTRATION: Clinicaltrials.gov NCT00990067.

  1. Enantiomeric profiling of chiral drug biomarkers in wastewater with the usage of chiral liquid chromatography coupled with tandem mass spectrometry.

    Castrignanò, Erika; Lubben, Anneke; Kasprzyk-Hordern, Barbara

    2016-03-18

    This paper proposes a novel multi-residue enantioselective method utilising a CBH (cellobiohydrolase) column, for the analysis of 56 drug biomarkers in wastewater. These are: opioid analgesics, amphetamines, cocaine, heroin, stimulants, anaesthetics, sedatives, anxiolytics, designer drugs, phosphodiesterase-5 (PDE5) inhibitors, amphetamine and methamphetamine drug precursors. Satisfactory enantiomeric separation was obtained for 18 pairs of enantiomers including amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and its metabolites HMA (4-hydroxy-3-methoxyamphetamine) and HMMA (4-hydroxy-3-methoxy-methamphetamine), PMA (para-methoxyamphetamine), MDA ((±)- 3,4-methylenedioxyamphetamine) and mephedrone. The method was applied in a one week monitoring study of a large wastewater treatment plant in the UK. Most target drugs were found at quantifiable concentrations in analysed samples. Enantiomeric profiling revealed that amphetamine, methamphetamine and MDMA were found enriched with R-(-)-enantiomers, probably due to their stereoselective metabolism favouring S-(+)-enantiomers. MDA was either enriched with R-(-)- or S-(+)-enantiomer indicating that its presence might be due to either abuse of racemic MDA or abuse of racemic MDMA respectively. Non-racemic enantiomeric fractions were also observed in the case of HMMA and mephedrone suggesting enantioselective metabolism. To the authors' knowledge, this is the first time chiral separation and wastewater profiling of mephedrone, PMA, MDMA and its metabolites HMA and HMMA have been reported. PMID:26896918

  2. Ecstasy tablets intoxication with lethal autcome

    Đorđević Snežana

    2007-01-01

    Full Text Available Background. Ecstasy, 3,4-methylenedioxymethamphetamine (MDMA, is a synthetic compound increasingly popular as a recreational drug. Tablets known as ecstasy contain MDMA, but may also contain caffeine, ephedrine, paramethoxyamphetamine, 3,4-methylenedioxyamphetamine (MDA, amphetamine, methamphetamine, and ketamine. After absorption MDMA is metabolized to MDA, 4-hydroxy-3- metoxymetamphetamine (HMMA and 4-hydroxy-3- metoxyamphetamine (HMA. After that HMMA and HMA are conjugated and excreted by urine. The aim of this report was to confirm by toxicological post mortem analyses of poisoned person organs that ecstasy had been the cause of his death. Case report. We reported the death of a 17-year-old boy after the ingestion of ecstasy. MDMA and metabolites were determined by multicolumn high performance liquid chromatography with UV spectral detection (HPLC-UV. Toxicological tests showed the presence of MDMA in all samples. When examining post mortem material (the organs, the highest concentrations were measured in the stomach (835,97 μg/g and kidney (801,14 μg/g. The minimal concentration was in the liver (22,26 μg/g. Conclusion. The obtained results of MDMA and its metabolites concentrations showed abuse of a high dose of ecstasy. .

  3. Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water.

    Evans, Sian E; Bagnall, John; Kasprzyk-Hordern, Barbara

    2016-08-01

    This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4-methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+)-enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+)-methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA. PMID:27182976

  4. Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenyl alkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

    Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenyl alkylamine designer drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy ethylamphetamine (MDEA), N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), 3,4-methylenedioxyamphetamine (MDA), and 3,4-(methylenedioxyphenyl)-2-butanamine (BDB), are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA) anhydride and analyzed by gas chromatography/mass spectrometry using electron ionization in positive mode. Gas chromatographic separation for TFA derivatives of all compounds was successfully resolved using an Equity-5 fused silica capillary column with a poly (5% diphenyl-95% dimethylsiloxane) stationary phase. Base peaks or prominent peaks of MA, AM, MDMA, MDEA, MBDB, MDA, and BDB appeared at m/z 154, 140, 154, 168, 168, 135, and 135, respectively. These occurred due to a-cleavage from the amide nitrogen, splitting into the TFA imine species and benzyl or methylenedioxybenzyl cations. Further prominent fragment ions at m/z 118 for MA and AM, m/z 162 for MDMA, MDEA, and MDA, and m/z 176 for MBDB and BDB were produced by cleavage of the phenylpropane or methylenedioxy propane hydrocarbon radical cation via a hydrogen rearrangement. These fragmentation pathways for the TFA derivatives of all the compounds are summarized and illustrated in this paper.

  5. Synthesis of [13C6]-labelled phenethylamine derivatives for drug quantification in biological samples.

    Karlsen, Morten; Liu, HuiLing; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bård Helge

    2014-05-15

    The availability of high-quality (13)C-labelled internal standards will improve accurate quantification of narcotics and drugs in biological samples. Thus, the synthesis of 10 [(13)C6]-labelled phenethylamine derivatives, namely amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-N-ethylamphetamine, 4-methoxyamphetamine, 4-methoxymethamphetamine, 3,5-dimethoxyphenethylamine 4-bromo-2,5-dimethoxyphenethylamine and 2,5-dimethoxy-4-iodophenethylamine, have been undertaken. [(13)C6]-Phenol proved to be an excellent starting material for making (13)C-labelled narcotic substances in the phenethylamine class, and a developed Stille-type coupling enabled an efficient synthesis of the 3,4-methylenedioxy and 4-methoxy derivatives. The pros and cons of alternative routes and transformations are also discussed. The [(13)C6]-labelled compounds are intended for use as internal standards in forensic analysis, health sciences and metabolomics studies by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. PMID:24634286

  6. Determination of drugs of abuse in blood.

    Moeller, M R; Steinmeyer, S; Kraemer, T

    1998-08-21

    The detection and quantitation of drugs of abuse in blood is of growing interest in forensic and clinical toxicology. With the development of highly sensitive chromatographic methods, such as high-performance liquid chromatography (HPLC) with sensitive detectors and gas chromatography-mass spectrometry (GC-MS), more and more substances can be determined in blood. This review includes methods for the determination of the most commonly occurring illicit drugs and their metabolites, which are important for the assessment of drug abuse: Methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), N-ethyl-3,4-methylenedioxyamphetamine (MDEA), 3,4-methylenedioxy-amphetamine (MDA), cannabinoids (delta-9-tetrahydrocannabinol, 11-hydroxy-delta-9-tetrahydrocannabinol, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol), cocaine, benzoylecgonine, ecgonine methyl ester, cocaethylene and the opiates (heroin, 6-monoacetylmorphine, morphine, codeine and dihydrocodeine). A number of drugs/drug metabolites that are structurally close to these substances are included in the tables. Basic information about the biosample assayed, work-up, GC column or LC column and mobile phase, detection mode, reference data and validation data of each procedure is summarized in the tables. Examples of typical applications are presented. PMID:9700554

  7. Simultaneous enantioselective determination of amphetamine and congeners in hair specimens by negative chemical ionization gas chromatography-mass spectrometry.

    Martins, Liliane; Yegles, Michel; Chung, Heesun; Wennig, Robert

    2005-10-15

    Enantioselective quantification of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) enantiomers in hair using gas chromatography-mass spectrometry (GC-MS) is described. Hair specimens were digested with 1M sodium hydroxide at 100 degrees C for 30 min and extracted by a solid phase procedure using Cleanscreen ZSDAU020. Extracted analytes were derivatised with (S)-heptafluorobutyrylprolyl chloride and the resulting diastereoisomers were quantified by GC-MS operating in the negative chemical ionization mode. Extraction yields were between 73.0 and 97.9%. Limits of detection varied in the range of 2.1-45.9 pg/mg hair, whereas the lowest limits of quantification varied between 4.3 and 91.8 pg/mg hair. Intra- and inter-assay precision and respective accuracy were acceptable. The enantiomeric ratios (R versus S) of AM, MA, MDA, MDMA and MDEA were determined in hair from suspected amphetamine abusers. Only MA and AM enantiomers were detectable in this collective and the quantification data showed in most cases higher concentrations of (R)-MA and (R)-AM than those of the corresponding (S)-enantiomers. PMID:16154523

  8. Evaluation of drug incorporation into hair segments and nails by enantiomeric analysis following controlled single MDMA intakes.

    Madry, Milena M; Steuer, Andrea E; Hysek, Cédric M; Liechti, Matthias E; Baumgartner, Markus R; Kraemer, Thomas

    2016-01-01

    Incorporation rates of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) into hair and nails were investigated after controlled administration. Fifteen subjects without MDMA use received two doses of 125 mg of MDMA. Hair, nail scrapings, and nail clippings were collected 9-77 days after the last administration (median 20 days). Hair samples were analyzed in segments of 1- to 2-cm length. After chiral derivatization with N-(2,4-dinitro-5-fluorophenyl)-L-valinamide, MDMA and MDA diastereomers were analyzed by liquid chromatography-tandem mass spectrometry. Highest concentrations in hair segments corresponded to the time of MDMA intake. They ranged from 101 to 3200 pg/mg and 71 to 860 pg/mg for R- and S-MDMA, and from 3.2 to 116 pg/mg and 4.4 to 108 pg/mg for R- and S-MDA, respectively. MDMA and MDA concentrations in nail scrapings and clippings were significantly lower than in hair samples. There was no significant difference between enantiomeric ratios of R/S-MDMA and R/S-MDA in hair and nail samples (medians 2.2-2.4 for MDMA and 0.85-0.95 for MDA). Metabolite ratios of MDA to MDMA were in the same range in hair and nail samples (medians 0.044-0.055). Our study demonstrates that administration of two representative doses of MDMA was detected in the hair segments corresponding to the time of intake based on average hair growth rates. MDMA was detected in all nail samples regardless of time passed after intake. Comparable R/S ratios in hair and nail samples may indicate that incorporation mechanisms into both matrices are comparable. PMID:26521178

  9. Comparison of hollow fiber liquid-phase microextraction and ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction for the determination of drugs of abuse in biological samples by gas chromatography-mass spectrometry.

    Meng, Liang; Zhang, Wenwen; Meng, Pinjia; Zhu, Binling; Zheng, Kefang

    2015-05-01

    Two microextraction techniques based on hollow fiber liquid-phase microextraction (HF-LPME) and ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME) had been applied for the determination of drugs of abuse (methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, methcathinone, ketamine, meperidine, and methadone) in urine and blood samples by gas chromatography-mass spectrometry. Parameters affecting extraction efficiency have been investigated and optimized for both methods. Under the optimum conditions, linearities were observed for all analytes in the range 0.0030-10 μg/ml with the correlation coefficient (R) ranging from 0.9985 to 0.9995 for HF-LPME and in the range 0.0030-10 μg/ml with the R ranging from 0.9985 to 0.9994 for DLLME. The recovery of 79.3-98.6% with RSDs of 1.2-4.5% was obtained for HF-LPME, and the recovery of 79.3-103.4% with RSDs of 2.4-5.7% was obtained for DLLME. The LODs (S/N=3) were estimated to be in the range from 0.5 to 5 ng/ml and 0.5 to 4 ng/ml, respectively. Compared with HF-LPME, the UA-LDS-DLLME technique had the advantages of less extraction time, suitability for batches of sample pretreatment simultaneously, and higher extraction efficiency, while HF-LPME has excellent sample clean-up effect, and is a robust and suitable technique for various sample matrices with better repeatability. Both methods were successfully applied to the analysis of drugs of abuse in real human blood sample. PMID:25801996

  10. Autoradiographic localization of 3H-paroxetine-labeled serotonin uptake sites in rat brain

    Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin

  11. Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

    The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism of MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg-1 sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences

  12. Autoradiographic localization of /sup 3/H-paroxetine-labeled serotonin uptake sites in rat brain

    De Souza, E.B.; Kuyatt, B.L.

    1987-01-01

    Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin.

  13. Simultaneous determination in hair of multiclass drugs of abuse (including THC) by ultra-high performance liquid chromatography-tandem mass spectrometry.

    Di Corcia, D; D'Urso, F; Gerace, E; Salomone, A; Vincenti, M

    2012-06-15

    A simple procedure for the quantitative determination in hair samples of 13 common drugs of abuse or metabolites (morphine, 6-acetylmorphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, benzoylecgonine, cocaine, buprenorphine, methadone and Δ(9)-tetrahydrocannabinol) has been developed and fully validated. The analytes were extracted from the matrix by a simple overnight incubation with methanol at 55 °C. An aliquot of the extract was directly injected into an ultra-high performance liquid chromatography system equipped with Waters Acquity UHPLC BEH C18 column (100 mm × 2.1mm, 1.7 μm). The mobile phase eluted with a linear gradient (water/formic acid 5 mM:acetonitrile; v:v) from 98:2 to 0:100 in 4.5 min, followed by isocratic elution at 100% B for 1.0 min. The flow rate was 0.6 mL/min and the total run time was 8.0 min including re-equilibration at the initial conditions. The compounds were revealed by a triple quadrupole mass spectrometer operating in the selected reaction monitoring mode. The absence of matrix interferents, together with excellent repeatability of both retention times and relative abundances of diagnostic transitions, allowed the correct identification of all analytes tested. The method proved linear in the interval from the limit of quantification to 5.0 ng/mg (1.0 ng/mg for Δ⁹-tetrahydrocannabinol) with correlation coefficient values ranging from 0.9970 to 0.9997. Quantitation limits were below the cut-off values recommended by the Society of Hair Testing and ranged from 0.02 to 0.08 ng/mg. Application of the present UHPLC-MS/MS procedure and instrumentation to hair analysis allows high sample-throughput, together with excellent sensitivity and selectivity, in workplace drug-screening controls and forensic investigations. These qualities, combined with minimal sample workup, make the cost of this screening affordable for most private and

  14. Repeated exposure to methamphetamine, cocaine or morphine induces augmentation of dopamine release in rat mesocorticolimbic slice co-cultures.

    Takayuki Nakagawa

    Full Text Available Repeated intermittent exposure to psychostimulants and morphine leads to progressive augmentation of its locomotor activating effects in rodents. Accumulating evidence suggests the critical involvement of the mesocorticolimbic dopaminergic neurons, which project from the ventral tegmental area to the nucleus accumbens and the medial prefrontal cortex, in the behavioral sensitization. Here, we examined the acute and chronic effects of psychostimulants and morphine on dopamine release in a reconstructed mesocorticolimbic system comprised of a rat triple organotypic slice co-culture of the ventral tegmental area, nucleus accumbens and medial prefrontal cortex regions. Tyrosine hydroxylase-positive cell bodies were localized in the ventral tegmental area, and their neurites projected to the nucleus accumbens and medial prefrontal cortex regions. Acute treatment with methamphetamine (0.1-1000 µM, cocaine (0.1-300 µM or morphine (0.1-100 µM for 30 min increased extracellular dopamine levels in a concentration-dependent manner, while 3,4-methylenedioxyamphetamine (0.1-1000 µM had little effect. Following repeated exposure to methamphetamine (10 µM for 30 min every day for 6 days, the dopamine release gradually increased during the 30-min treatment. The augmentation of dopamine release was maintained even after the withdrawal of methamphetamine for 7 days. Similar augmentation was observed by repeated exposure to cocaine (1-300 µM or morphine (10 and 100 µM. Furthermore, methamphetamine-induced augmentation of dopamine release was prevented by an NMDA receptor antagonist, MK-801 (10 µM, and was not observed in double slice co-cultures that excluded the medial prefrontal cortex slice. These results suggest that repeated psychostimulant- or morphine-induced augmentation of dopamine release, i.e. dopaminergic sensitization, was reproduced in a rat triple organotypic slice co-cultures. In addition, the slice co-culture system revealed that the NMDA

  15. Validação de método para determinação de 3,4-metilenodioximetanfetamina (MDMA em comprimidos de ecstasy por cromatografia em fase gasosa Validation of a gas-chromatographic method for the determination of 3,4-methylenedioxymethamphetamine(MDMA in ecstasy tablets

    Silvio Fernandes Lapachinske

    2004-03-01

    , 3,4-methylenedioxyamphetamine (MDA, methamphetamine and amphetamine have already been identified in ecstasy tablets. Caffeine and ephedrines are the most common adulterants also found. The aim of this paper is to describe the validation of an analytical method to quantify MDMA in ecstasy tablets and capsules. Gas-chromatography with nitrogen/phosphorous detector was used in the method, which consisted in the direct dissolution of the sample in methanol, centrifugation and convenient dilution of the supernatant. Analog substances to MDMA and adulterants were also identified. The limits of detection and quantification (LOQ and LOD for MDMA were 1.5 and 3.0 mg/100 mg of tablet. Samples from 25 lots of tablets seized in the city of São Paulo were analyzed showing a considerable variability in composition and quantity of MDMA.

  16. Desenvolvimento e validação de um método cromatográfico em fase gasosa para análise da 3,4-metilenodioximetanfetamina (ecstasy e outros derivados anfetamínicos em comprimidos Development and validation of a gas chromatography method for determination of ecstasy and amphetamines derivatives in tablets

    Marcelo Carvalho Lasmar

    2007-06-01

    Full Text Available O uso abusivo das anfetaminas e seus derivados vêm aumentando dramaticamente nos últimos anos em diversas regiões do mundo, notando-se especial utilização do Ecstasy. A análise de amostras da droga apreendidas nas ruas evidenciou, além da presença de MDMA (3,4-metilenodioximetanfetamina, componente principal da droga, outras feniletilaminas, como a MDA (3,4-metilenodioxanfetamina e MDEA (metilenodioximetiletilanfetamina este último também conhecido como a droga Eve, ainda pouco difundida no Brasil. O objetivo do presente trabalho foi desenvolver e validar um método analítico confiável, prático e acessível aos laboratórios de toxicologia, de médio e pequeno porte, no Brasil e em países em desenvolvimento, para identificação separada do MDMA, MDA e MDEA. A cromatografia em fase gasosa utilizando-se coluna capilar e detector de ionização de chama foi a técnica escolhida. O método analítico apresentou para os três analitos de interesse, faixa ampla de linearidade (1,0 a 500,0 µg/mL; limites de quantificação de 1,0 µg/mL e coeficientes de variação intra e interensaio inferiores a 9,5%. Os limites de detecção estabelecidos foram 0,7 µg/mL, 0,8 µg/mL e 0,6 µg/mL, respectivamente para o MDMA, MDA e MDEA. O método foi seletivo na presença de epinefrina, cocaína, anfetamina, ácido acetilsalisílico, metanfetamina, ácido dietilbarbitúrico, p-aminobenzoil dietilbarbitúrico, paracetamol e cafeína.The abusive use of the amphetamine derivative ecsyasy in the world come increasing in the last years. Many tablets samples kept on the streets shown the presence not only of the MDMA- 3,4-methylenedioxymethamphetamine, the main drug component but also of the MDA - 3,4- methylenedioxyamphetamine and MDEA - 3,4-methylenedioxymethylethylamphetamine. The present study sought to develop and validate an analytical method for determination of MDMA, MDA and MDEA in tablets to be accessible for the most small or medium