3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") 3' is a 'psychedelic amphetamine' that has gained popularity over the past 20 years because of its ability to produce strong feelings of comfort, empathy, and connection to others. MDMA analysis in blood and urine samples have been consistently used for clinical pharmacology studies and forensic science cases. However, new developments in clinical toxicology require new analytical approaches and the use of alternative biological matrices for establishing whether individuals have consumed the drug, when and/or if they have been acting under the effect of the drug.It is postulated that MDMA physic-chemical properties: (i) pKa of around 9.9 corresponding to a weak base that facilitates the transfer of MDMA from plasma (pH=7.4) to fluids/matrices with a favourable pH gradient, (ii) high liposolubility with volumes of distribution between 6 and 7 liters per kilogram, (iii) low protein binding, favour its distribution to biological matrices in humans. Several non-conventional biological matrices such as hair, sweat and saliva, because of drug accumulation due to its physico-chemical properties, might be of use for the detection of past and recent exposure to MDMA.Three different studies were set-up. The study 1 investigating the pharmacokinetics of MDMA in saliva after a single oral dose administration of 100 mg to eight healthy volunteers, the second investigating the pharmacokinetics of MDMA in sweat after a single dose administration of 100 mg to eight healthy volunteers, and finally a study on segmental analysis of MDMA in hair of thirteen drug consumers with different patterns of consumption..The first study evidenced that MDMA is excreted in saliva, after a single 100 mg dose administration, with concentrations (range 1728.9-6510 µg/ml at 1.5 h after drug intake) one order of magnitude higher than those observed in plasma (range 134.9-223 µg/ml at 1.5 h after drug intake) and following a time course kinetics which parallels that of plasma and that of subjective effects and psychomotor performance. On-site testing by Drugwipe device proved suitable to detect individuals under the influence of drug effects in the first 6 hours after drug intake by non-invasive and rapid collection of salivary specimens.The second study showed that MDMA appears in sweat and can be quantified already in the first few hours after a single dose administration, when subjective effects are apparent (concentration range 3.2-1326 ng/pacth). This result makes:the sweat patch technology useful for monitoring MDMA accumulation in sweat at least during the 24 hours after a single administration, On-site sweat testing by drugwipe device suitable to detect individuals under the influence of drug effects by non-invasive and rapid collection of minute amounts of sweat.MDMA appears in hair from consumers (concentration range 1.2-12.6 ng/mg hair) and can be detected in hair segments corresponding to the last one, six and twelve month of repeated drug use. For this reason:Hair analysis of MDMA can be used to evaluate exposure or abstinence to the drug in the last months, hair concentration of MDMA in different hair segments can predict levels of drug use(r2=0.92) and can be eventually associated to chronic psychophysical effects induced by the repeated drug use.The measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations both in clinical and toxicological studies A common characteristic of the three different matrices is that the parent drug MDMA was always the principal, most abundant analyte detected, whose concentration could be associated with drug-induced effects and drug history. As already assessed, drug analysis in hair extends the information of drug consumption to a wider time-window than that of other non-invasive biological matrices, such as saliva and sweat. These latter two matrices can account for acute pharmacological effects induced by the drug, while results from hair testing can be used to assess repeated exposure to drug and eventual association with long term drug induced effects, such as neurotoxicity and psychological performance in the specific case of MDMA.

O propósito do estudo realizado foi de investigar o comportamento voltamétrico da 3,4-metilenodioximetanfetamina (MDMA), substância psicoativa do ecstasy, uma droga que tem se tornado cada vez mais popular entre os usuários de drogas. Empregou-se o uso da técnica de cromatografia líquida de alta eficiência, para isolar a substância a partir de amostras de ecstasy obtidas em parceria com a Polícia Científica de Ribeirão Preto, bem como a técnica de espectrometria de massas, para confirmar a presença da MDMA nas mesmas. Os estudos voltamétricos foram realizados utilizando-se um sistema de três eletrodos, sendo o eletrodo de trabalho de carbono vítreo, eletrodo de referência Ag/AgCl e eletrodo auxiliar de fio de platina. O comportamento eletroquímico desta substância foi investigado diante de diferentes modalidades voltamétricas: Voltametria cíclica, de pulso diferencial e de onda quadrada, nas quais se pôde observar um pico anódico em Ep = +1,1 V. Foram otimizados os parâmetros voltamétricos de modo a tornar a análise mais rápida e sensível, sem perda de intensidade e qualidade do sinal voltamétrico. Com os parâmetros voltamétricos otimizados, foram construídas curvas analíticas para o analito em questão nas diferentes modalidades voltamétricas estudadas. Foi possível determinar o teor de MDMA nas cinco diferentes amostras de ecstasy utilizadas, das quais quatro apresentaram MDMA com teores variando de 3 a 10% (m/m) e uma na qual não foi constatada a presença da droga, mas sim de outro fármaco, a lidocaína. / The main purpose of the present study was to investigate the voltammetric behavior of 3,4-methylenedioxymethanphetamine (MDMA), the psychoactive substance of ecstasy, a drug that has become increasingly popular among drug users. The high performance liquid chromatography technique was employed in order to isolate the substance from ecstasy samples obtained in partnership with Polícia Científica de Ribeirão Preto and also the mass spectrometry technique was employed to confirm the presence of MDMA. The voltammetric studies were performed using the three electrodes system, being glassy carbon as the working electrode, Ag/AgCl as the reference electrode and platinum wire as counter electrode. The electrochemical behavior of the substance was investigated using different voltammetric techniques: Cyclic, differential pulse and square wave voltammetry modalities, in which an anodic peak was observed at Ep = +1,1 V. The voltammetric parameters were optimized in order to make the analysis faster and more sensitive, without loss of quality and intensity of the voltammetric signal. With the voltammetric parameters optimized, analytical curves of the studied analyte were built for the different voltammetric techniques. It was possible to determine the content of MDMA in the five different ecstasy samples utilized, in which four showed MDMA with contents ranging from 3 to 10% (m/m) and one in which no MDMA was observed but another drug, lidocaine.

O propósito do estudo realizado foi de investigar o comportamento voltamétrico da 3,4-metilenodioximetanfetamina (MDMA), substância psicoativa do ecstasy, uma droga que tem se tornado cada vez mais popular entre os usuários de drogas. Empregou-se o uso da técnica de cromatografia líquida de alta eficiência, para isolar a substância a partir de amostras de ecstasy obtidas em parceria com a Polícia Científica de Ribeirão Preto, bem como a técnica de espectrometria de massas, para confirmar a presença da MDMA nas mesmas. Os estudos voltamétricos foram realizados utilizando-se um sistema de três eletrodos, sendo o eletrodo de trabalho de carbono vítreo, eletrodo de referência Ag/AgCl e eletrodo auxiliar de fio de platina. O comportamento eletroquímico desta substância foi investigado diante de diferentes modalidades voltamétricas: Voltametria cíclica, de pulso diferencial e de onda quadrada, nas quais se pôde observar um pico anódico em Ep = +1,1 V. Foram otimizados os parâmetros voltamétricos de modo a tornar a análise mais rápida e sensível, sem perda de intensidade e qualidade do sinal voltamétrico. Com os parâmetros voltamétricos otimizados, foram construídas curvas analíticas para o analito em questão nas diferentes modalidades voltamétricas estudadas. Foi possível determinar o teor de MDMA nas cinco diferentes amostras de ecstasy utilizadas, das quais quatro apresentaram MDMA com teores variando de 3 a 10% (m/m) e uma na qual não foi constatada a presença da droga, mas sim de outro fármaco, a lidocaína. / The main purpose of the present study was to investigate the voltammetric behavior of 3,4-methylenedioxymethanphetamine (MDMA), the psychoactive substance of ecstasy, a drug that has become increasingly popular among drug users. The high performance liquid chromatography technique was employed in order to isolate the substance from ecstasy samples obtained in partnership with Polícia Científica de Ribeirão Preto and also the mass spectrometry technique was employed to confirm the presence of MDMA. The voltammetric studies were performed using the three electrodes system, being glassy carbon as the working electrode, Ag/AgCl as the reference electrode and platinum wire as counter electrode. The electrochemical behavior of the substance was investigated using different voltammetric techniques: Cyclic, differential pulse and square wave voltammetry modalities, in which an anodic peak was observed at Ep = +1,1 V. The voltammetric parameters were optimized in order to make the analysis faster and more sensitive, without loss of quality and intensity of the voltammetric signal. With the voltammetric parameters optimized, analytical curves of the studied analyte were built for the different voltammetric techniques. It was possible to determine the content of MDMA in the five different ecstasy samples utilized, in which four showed MDMA with contents ranging from 3 to 10% (m/m) and one in which no MDMA was observed but another drug, lidocaine.

La MDMA és cap de sèrie dels entactògens. El seu consum provoca toxicitat aguda i neurodegeneració a mig/llarg termini del sistema serotoninèrgic. Es postula que la bioactivació metabòlica podria ser responsable del desenvolupament de neurotoxicitat.La MDMA té un centre estereogènic. Es consumeix com a racemat, però els enantiòmers tenen perfils farmacològics diferenciats. A més, la MDMA té una depuració metabòlica enantioselectiva i autoinhibible (CYP2D6). Aquesta tesi presenta l'enantioselectivitat de la depuració metabòlica de la MDMA en consumidors recreatius participants d'un assaig clínic (dosi: 100 mg).Es sintetitzà material de referència i es desenvolupà metodologia per a l'anàlisi enantioselectiu i diastereoselectiu dels compostos.S'estudià l'enantioselectivitat en el metabolisme fins a 48h post-administració, obtenint-se raons (R)-MDMA/(S)-MDMA>1 i en augment amb el temps. Les raons del metabòlits majoritaris foren pràcticament constants i properes a 1, possiblement degut a la inhibició metabòlica del CYP2D6 i a la participació d'altres enzims no enantioselectius. / La MDMA es la cabeza de serie de los entactógenos. Su consumo provoca toxicidad aguda y neurodegeneración serotonérgica a medio/corto plazo. Se postula que una bioactivación metabólica podría ser responsable del desarrollo de neurotoxicidad.La MDMA tiene un centro estereogénico. Se consume como racemato, pero los enantiómeros tienen perfiles farmacológicos diferenciados. Además, presenta depuración metabólica enantioselectiva y autoinhibible (CYP2D6).Esta tesis presenta la enantioselectividad de la depuración metabólica de la MDMA en consumidores recreativos participantes de un ensayo clínico (dosis: 100 mg).Se sintetizó material de referencia y se desarrolló metodología para el análisis enantioselectivo y diastereoselectivo de los compuestos.Se estudió la enantioselectividad en el metabolismo hasta 48h post-administración, obteniéndose relaciones (R)-MDMA/(S)-MDMA>1 y en aumento con el tiempo. Las relaciones de los metabolitos mayoritarios fueron prácticamente constantes y cercanas a 1, posiblemente debido a la inhibición metabólica del CYP2D6 y a la participación de otros enzimas no enantioselectivos. / MDMA is the head of entactogenic compounds. Its consumption causes acute toxicity and mid/long term serotonergic neurodegeneration. It is postulated that a metabolic bioactivation may be responsible for development of neurotoxicity.MDMA has a stereogenic center. It is consumed as a racemate, but its enantiomers have different pharmacological profiles. Also, MDMA presents an enantioselective and self-inhibited metabolic disposition (CYP2D6).The present thesis shows data about enantioselective metabolic disposition of MDMA in recreative consumers that participated in a clinical trial (dose: 100 mg).It was synthesised reference material and it was developed methodology for both enantioselective and diastereoselective analysis MDMA and its main metabolites.It was studied the enantioselectivity in the metabolism after 48h post-administration. (R)-MDMA/(S)-MDMA ratios were >1 and increasing over time. Major metabolites ratios were practically constant and close to 1, possibly because of the metabolic inhibition of CYP2D6 and the role of other non-enantioselective enzymes.