Desenvolvimento e aplicação de método analí­tico para detecção de estimulantes em suplementos nutricionais adulterados / The development and application of analytical method for the detection of stimulants in adulterated nutritional supplements

A adição fraudulenta de ativos farmacêuticos em suplementos nutricionais é um problema mundial. É comum encontrar mensagens sobre perda de peso, aumento da capacidade intelectual e/ou física, e estímulo sexual na embalagem de suplementos adulterados com fármacos sintéticos ocultos em formulações aparentemente inofensivas para os usuários. No Brasil, a disponibilidade de dados sobre a adulteração de suplementos nutricionais é escassa. No presente trabalho, foi desenvolvido e aplicado um método analítico empregando cromatografia gasosa com detector de nitrogênio fósforo (GC-NPD) para a detecção, identificação e quantificação de estimulantes/anorexígenos não declarados nos rótulos de suplementos alimentares, tais como: cafeína, femproporex, anfepramona, fenfluramina, sibutramina, fentermina, efedrina, fenilpropanolamina, pseudoefedrina e 4- metilhexan-2-amina. A técnica de extração/solubilização com metanol foi utilizada, ressaltando a utilização de baixa quantidade de amostra, solvente e padrões de estimulantes. Após o desenvolvimento e validação do método, as análises foram aplicadas em amostras de suplementos nutricionais obtidos em lojas especializadas em suplementos, de diversas partes do estado de São Paulo (n=125). Das 125 amostras de suplemento nutricional analisadas, 38 delas (30%) apresentaram resultado positivo para alguma das substâncias de interesse, dentre elas, sibutramina, cafeína e efedrina mediante a metodologia escolhida. As amostras positivas foram posteriormente analisadas qualitativamente por LC-MS/MS, no propósito de confirmar o resultado positivo obtido. A técnica analítica empregada proporciona seletividade, linearidade, precisão, exatidão, recuperação e limites em conformidade ao objetivo que foram destinadas. Os métodos de preparo de amostra desenvolvidos e validados demonstraram ser simples, práticos, eficientes e diferenciados pelo baixo uso de amostra e solvente

The fraudulent addition of active pharmaceutical compounds in nutritional supplements is, indeed, a worldwide problem. Often, it can be found several advertisements on various supplement packaging assuring weight loss, increased intellectual and/or physical capacity and sexual stimulation. These products may have been 'spiked' with synthetic drugs containing formulations which are apparently harmless to users. In Brazil, the availability of data about adulteration of nutritional supplements is scarce. In the present work, an analytical method using gas chromatography coupled with a nitrogen-phosphorus detector (GC-NPD) was developed and applied for the detection, identification and quantification of undeclared stimulants and/or anorectic agents in food supplement labels, such as: caffeine, fenproporex, amfepramone, fenfluramine, sibutramine, phentermine, ephedrine, phenylpropanolamine, pseudoephedrine e 4- metilhexan -2- amine. The extraction/solubilization with methanol presented satisfactory results, emphasizing the use of low amount of sample, solvent and standards of analytes. After the development and validation, the method was applied in samples of nutritional supplements obtained from specialty stores in various parts of the state of São Paulo (n = 125). From the 125 nutritional supplement samples analyzed, 38 of them (30%) presented positive results for some of the substances of interest, among them sibutramine, caffeine and ephedrine according to the chosen methodology. The positive samples were subsequently analyzed qualitatively by LCMS / MS, in order to confirm the positive result obtained. The analytical technique employed provides selectivity, linearity, precision, accuracy, recovery and limits in accordance with the intended purpose. The sample preparation methods developed and validated to be simple, practical, efficient and differentiated by the low sample and solvent usage

Cross-sectional study of the dispensation of synthetic anorectic drugs in community pharmacies in the city of Cruz Alta - State of Rio Grande do Sul

Obesity is defined as the excess adipose tissue in the body. Drugs responsible for inhibiting the appetite are called anorectics or appetite suppressants. Sibutramine, fenproporex and amfepramone belongs to this class, and are capable of causing physical or psychological dependence. The aim of this study was to evaluate the frequency of prescriptions for appetite suppressants in community pharmacies at Cruz Alta, State of Rio Grande do Sul, Brazil. The sales of fenproporex, amfepramone and sibutramine in the months of September, October and November 2010 and April, May and June 2011 were compared. It was observed that the most commonly dispensed anorectic in the three community pharmacies analyzed was sibutramine. In the months of September, October and November 2010, consumption was higher, with sibutramine achieving 40.3% of overall sales, amfepramone 21% and, finally, fenproporex, 7.9%. The consumption of appetite suppressants was more prevalent in females, who represented 82% of total. The results suggested the existence of high consumption of anorectics, possibly related to the current concern with aesthetic standards, which emphasizes the importance of strict control over the marketing of these substances.

Obesidade define-se como excesso de tecido adiposo no organismo. Os fármacos responsáveis por inibir o apetite são denominados anorexígenos ou supressores de apetite. Sibutramina, femproporex e anfepramona, pertencentes a essa classe, são capazes de provocar dependência física ou psíquica. O objetivo deste estudo foi avaliar a prevalência da prescrição de anorexígenos em farmácias comerciais de Cruz Alta - RS. Foi comparada a venda dos fármacos femproporex, anfepramona e sibutramina, nos meses de setembro, outubro e novembro de 2010 e abril, maio e junho de 2011. Observou-se que o anorexígeno mais prescrito nas três farmácias analisadas foi a sibutramina. Nos meses de setembro, outubro e novembro de 2010, o consumo foi maior, quando a sibutramina alcançou um percentual de 40,3%, a anfepramona 21% e, por fim, o femproporex, 7,9%. O consumo de inibidores de apetite foi mais prevalente no sexo feminino, o qual representou 82% do total. Os resultados sugeriram a existência de elevado consumo de anorexígenos, possivelmente relacionada à preocupação com padrões estéticos atuais, o que ressalta a importância de um controle rigoroso sobre a comercialização destas substâncias.

A Case of Phendimetrazine Induced-Psychotic Disorder and Dependence / 신경정신의학

Phendimetrazine and related amphetamine-like compounds are used widely as appetite suppressants in Korea. We report on a patient who developed psychotic disorder and dependence while using phendimetrazine. A 25-year-old female with no psychiatric history began experiencing hallucination of bugs after using phendimetrazine for weight loss for five months. She was admitted and the drug was stopped. Three days later, her psychotic symptoms had subsided and she returned home. Two months after discharge, against medical advice, she returned to a clinic to obtain phendimetrazine for its anorectic effect. She continued using phendimetrazine because she had developed withdrawal symptoms and experienced cravings for it. Within two months of restarting the drug, she had developed paranoid delusions, auditory and olfactory hallucinations. She was readmitted, and was confirmed to have a dependence on phendimetrazine. This case provides a warning that amphetamine-related anorectics can cause psychotic disorder and dependence.