A common practice amongst street drug manufacturers and dealers is to combine the illicit drug of abuse they intend to distribute with additional substances. Substances added in an attempt to mimic or enhance the desired effect of the drug of abuse are known as adulterants as opposed to diluents, which are added simply to increase the weight of the product. By definition, an adulterant has a physiological effect on the body and as physiologically active compounds these adulterants may have side effects apart from the drug it is added to. They can be minimal, treatable, or otherwise manageable while others can be worse than those incurred from the drug of abuse itself. Due to varying trends in street drug purity, an effort must be made to understand the effects adulterants and diluents, as well as mixtures thereof, may have on forensic drug analysis. Colorimetric spot test analysis is typically performed using a representative sample of the raw, suspected drug material. These tests are often employed in the lab prior to any attempt to isolate a specific compound or at the scene before an arrest is made. This being the case, the reagents will be exposed to and have the potential to react with anything present in the sample with the drug of abuse. While much work has been done regarding the specificity and cross reactivity of colorimetric spot tests, limited information is available about how mixtures of adulterants may affect the results. This research consists of two parts which approach the common theme of adulterants differently. The first part is a literature based investigation into the pathological side effects of several common drug adulterants. The specific compounds discussed are: levamisole, phenacetin, atropine, and several topical anesthetics (benzocaine, lidocaine, prilocaine, and procaine). A review of articles from the scientific literature was conducted in order to convey what is known in the medical field regarding the effects these compounds can have on the body. The second part of this research was a laboratory based investigation which analyzed the effects of twenty-three common adulterants on two colorimetric spot tests: the Marquis reagent for the presumptive identification of heroin, morphine, amphetamine, methamphetamine, and 3,4-methylenedioxy-N-methamphetamine (MDMA) and the modified Scott test for the presumptive identification of cocaine. This was performed in order to observe the reactivity of these compounds so that a better understanding of the effect their presence can have on the analysis of seized drug samples using these tests could be obtained. The literature review portion of this research revealed that the adulterants levamisole, atropine, phenacetin, and the topical anesthetic adulterants lidocaine, prilocaine, benzocaine, and procaine, can be toxic and have severe, deleterious effects on the body in both chronic and acute exposures. Levamisole stimulates the immune system resulting in the production of self-reactive antibodies that attack neutrophils. This causes an autoimmune disorder that weakens the immune system and causes leukocyte agglutination leading to necrotizing vasculitis. Atropine functions to decrease the parasympathetic tone and increase the sympathetic tone in the body. An overdose can cause anticholinergic toxicity, a syndrome very similar to sympathomimetic toxidrome caused by cocaine overdose. Both are characterized by hypertension, hyperthermia, tachycardia, ataxia, disorientation, and mydriasis. However, they can be distinguished as anticholinergic toxicity causes dry and flush skin and mydriasis which is unreactive to light while sympathomimetic toxidrome causes profuse sweating and mydriasis which is reactive to light. Phenacetin is metabolized to O-ethyl-N-acetyl-p-benzoquinone imine (O-Et-NAPQI), a highly reactive and unstable electrophile. It is capable of covalently binding with proteins and other cellular components, including deoxyribonucleic acid (DNA). This leads to mutagenesis and subsequent tumor generation as well as apoptosis and necrosis of various tissues in the bladder and kidneys. The topical anesthetics have each been associated with the development of methemoglobinemia. This is a condition caused by an increase in the concentration of methemoglobin in the blood. Methemoglobin binds more strongly to oxygen so that it cannot be released to the tissues resulting in oxygen starvation. This was found to be caused by the metabolism of prilocaine and lidocaine to the oxidative compounds O-toluidine and 2,6-xylidine respectively. The cause has not been previously reported for benzocaine or procaine. The laboratory portion of this research revealed the impact several adulterants and their mixtures can have on colorimetric spot tests. Testing with approximately 1 mg of sample material revealed that eight out of the twenty-three adulterants reacted with the Marquis reagent to cause a color change within 15 minutes. Of the ten 3-component mixtures tested, eight resulted in a color change. Of the six five-component mixtures, four resulted in a color change; of the six eight-component mixtures, three resulted in a color change; and of the six ten-component mixtures, five resulted in a color change. Of the color changes observed, none were consistent with the "expected" color change for a presumptively positive result of the Marquis test. Testing with the adulterant diphenhydramine revealed that this compound had a unique and intense reaction with the Marquis reagent. This compound initially reacted by turning the liquid a vibrant yellow-green upon contact with the sample. Prior to 2 minutes, solid red-brown aggregates formed in the liquid and proceeded to increase in size while the reagent solution darkened to a red-black color over the 15 minutes of observation. Mixtures containing diphenhydramine each reacted differently. Solid material did not form in the mixture tests and the color changes observed ranged from light orange to a dark red-orange. In addition, one 3-component mixture containing adulterants which did not cause a color change when tested individually (diltiazem, acetaminophen, and quinine) was observed to cause a light brown color to develop, which darkened over the 15 minutes of observation. The results for the modified Scott test showed that the complexity of this test has made it highly specific for cocaine. None of the individual components or mixtures tested reacted in a manner consistent with a presumptively positive identification for cocaine hydrochloride (HCl) or cocaine base for all three steps. Of the twenty-three adulterants tested, eight of the twenty-three gave a similar result to cocaine base in step 1, however, of these eight, only one (quinine) gave a similar result to cocaine base in step 2, and this adulterant did not react consistently to cocaine base in step 3. The research using the adulterant mixtures revealed that the compounds present in these samples tended to react individually with the modified Scott test reagents. In other words, the results for each mixture appeared as a combination of the individual results for each component. While the results observed for the adulterants and mixtures tested were not consistent with the expected presumptively positive results for the drugs these tests are used to detect, it was concluded that the presence of adulterants in a sample has the potential to affect the results of a colorimetric spot test in a variety of ways. Given that these tests are typically employed on samples of raw suspected drug material, it is important that analysts understand the impact adulterants can have on the interpretation of presumptive drug tests.

The relationship of artificial heating to the germination of seeds has been a subject of more or less interest for the last 75 years. Like other research work, experimenters first had their attention called to the problem largely as the result of innate curiosity. They were interested in the result as measured by germinative power, of the application to seeds of different amounts of heat for varying periods of time, consequently many divergent and sundry experiments were carried out. Seeds of a large number of plants have been subjected to tests and the results recorded. The investigations include the effect of heating seeds in soil, in water, in atmospheres of different relative humidities, in carbon dioxid, in ether, in carbon disulphid and in dry air. Each specific experiment has been associated with various temperatures and with various periods of tiem. It is of interest to note that the actual methods used in determining results are about as diversified as the time and temperature. This thesis presents data showing only the effects of dry heating seed at high temperatures. Therefore in discussion of the literature only that material will be considered which has a direct bearing upon that phase of the heating problem.

Current screening methods for drug analysis with urine samples includes examination of the sample with an immunoassay. These methods are used to determine the concentration of drug metabolites contained within the sample prior to further confirmatory testing. Drug testing plays a crucial role in maintaining safe workplace environments and safety of individuals. However, a positive result can lead to heavy consequences for the employee including suspension or removal from the workplace. Therefore, a majority of individuals add commonly known products into the sample to evade detection by developing a false negative result. Although specimen integrity examinations are performed to identify tampering of the sample, these results are typically biased on the experience of the examiner. The purpose of this study was to develop an analytical screening technique that will detect the drug of interest as well as the presence of any additional products that may be added into the sample via Direct Analysis in Real Time – High Resolution/Mass Spectrometry (DART-HR/MS) which is an ambient ionization source that produces fast mass spectrum results that can provide semi-quantitative information of the target metabolite concentration. Although there are various studies that indicate the ability of the DART to detect drug compounds, there are no known studies that have examined how real-world urine samples are analyzed. Additionally, there are no current studies that take into consideration adulteration of the urine sample using the DART method. The results obtained in the study showed the ability for DART to identify molecular protonated peaks indicative of dextroamphetamine and/or the presence of masking agents. While the other target drugs could not be identified using this method, the identification of dextroamphetamine, adulterant products and the deuterated internal standard show promise in using this as a screening technique prior to confirmatory tests. Future work is currently being conducted to optimize the protocol for the evaluation of THC, cocaine and benzodiazepines.

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.

A alta prevalência de uso de cocaína, e o alarmante número de apreensões do entorpecente, trazem à tona a necessidade de se explorar novas formas de combate ao tráfico. A investigação dos componentes presentes nas amostras apreendidas tem sido bastante explorada, pois. para chegar ao consumidor final, a cocaína \"de rua\", além das etapas básicas de obtenção, muitas vezes é também submetida às etapas de adição de diluentes e de adulterantes. Sabendo-se que o maior número de laudos expedidos pelo Núcleo de Perícias Criminalísticas de Araçatuba é atribuído a exames relacionados com entorpecentes, e que para a cidade não há estudo a cerca dos componentes das amostras apreendidas de cocaína e suas referências geográficas, o presente trabalho teve por objetivo investigar os adulterantes presentes em 92 amostras de cocaína apreendidas na região de Araçatuba, no período de 2014 a 2015 empregando o método de extração líquido-líquido e análise por Cromatografia em fase Gasosa utilizando detector de Espectrometria de massas. Como resultado foram identificados, em ordem decrescente de recorrência, os adulterantes: cafeína, lidocaína, fenacetina, levamisol, carisoprodol, aminopirina, benzocaína metotrimeprazina e cloridrato de cetamina. Também foram identificados outros alcaloides como éster de metilecgonidina, cinamoilcocaínas e norcocaína. A maior parte das amostras analisadas demonstrou-se adulterada e em mais de 78% das amostras foi detectado o éster de metilecgonidina, substância formada a partir da pirólise, ou degradação térmica da cocaína. Foram elaborados mapas georreferenciados baseados nos sítios das apreensões, em que se pode visualizar que as mesmas ocorreram nas regiões periféricas das cidades abordadas, demonstrando a presença de três principais núcleos de densidade de apreensões, localizados na cidade de Araçatuba / The high prevalence of cocaine use, and its alarming number of seizures, shows the need to explore new tools for drug trafficking combat. Investigations about components presents in drug seized samples has been high explored, mainly because drug dealers used to add compounds on street cocaine, like diluents and adulterants. Knowing that the highest number of reports made on Núcleo de Perícias Criminalísticas de Araçatuba are related to narcotics, and that for this city there is no study about the components of the cocaine seized samples and its geographic references, the present work had the aim of investigating the adulterants present in 92 cocaine samples seized in the region of Araçatuba, from 2014 to 2015, using the method of liquid-liquid extraction and analysis by Gas Chromatography Mass Spectrometry. As a result, the adulterants identified: were caffeine, followed by lidocaine, phenacetin, levamisole, carisoprodol, aminopyrine, benzocaine methotrimeprazine and ketamine. Other alkaloids have also been identified as ecgonidine methy ester, cinnamoylcocaine and norcocaine. Most of the analyzed samples were adulterated and in more than 78% of them showed the presence of ecgonidine methyl ester, a compound formed from the cocaine pyrolysis, or thermal degradation. Georeferenced maps were made based on the seizure geographic coordinates, where it can be seen that they occurred in the peripheral regions of the cities, and the presence of three main seizure density areas, located in the city of Araçatuba.

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.

Linha de pesquisa: Tecnologia e vigil?ncia em sa?de. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-01-10T19:40:05Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) anderson_caldeira_oliveira.pdf: 1872739 bytes, checksum: 55f5678427b28e816e057b67c0d0cecc (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-01-19T17:14:17Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) anderson_caldeira_oliveira.pdf: 1872739 bytes, checksum: 55f5678427b28e816e057b67c0d0cecc (MD5) / Made available in DSpace on 2018-01-19T17:14:17Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) anderson_caldeira_oliveira.pdf: 1872739 bytes, checksum: 55f5678427b28e816e057b67c0d0cecc (MD5) Previous issue date: 2017 / O Brasil encontra-se entre os pa?ses de maior consumo de coca?na no mundo. As quest?es relacionadas ao uso da coca?na provocam preocupa??es, uma vez que s?o acompanhadas de consequ?ncias que atingem m?ltiplas dimens?es da sociedade moderna. Os problemas associados ao tr?fico e ao consumo de drogas est?o difundidos por todo o pa?s, alcan?ando, inclusive, munic?pios de pequeno porte. A presen?a de adulterantes pode ocasionar rea??es inesperadas bem como potencializar os danos ? sa?de dos usu?rios. Este trabalho teve como objetivo caracterizar amostras de coca?na apreendidas no munic?pio de Diamantina, Minas Gerais, quanto ao teor de coca?na e presen?a de adulterantes. Em uma primeira etapa do trabalho, foi validada uma metodologia anal?tica para quantifica??o de coca?na em amostras apreendidas com uso da Cromatografia Gasosa acoplada ? Espectrometria de Massas com monitoramento de ?ons selecionados (selected-ion monitoring - SIM) (CG-EM-SIM). Em uma segunda etapa, foram analisadas cento e vinte e nove amostras, sendo destas sessenta e sete apreendidas na forma de p? e sessenta e duas como crack. Foram realizadas an?lises para a identifica??o de adulterantes e para determina??o do teor de coca?na nas amostras, sendo a identifica??o de adulterantes realizada por Cromatografia Gasosa acoplada Espectrometria de Massas (CG-EM), no modo full scan, e a quantifica??o da coca?na por CG-EM?SIM. Foi realizada a compara??o do teor m?dio entre as amostras apreendidas na forma p? e de crack pelo teste U de Mann-Whitney. A fenacetina foi o principal adulterante encontrado. Outros adulterantes como benzoca?na, cafe?na, levamisol, lidoca?na e proca?na tamb?m foram detectados. As amostras apreendidas como crack apresentaram not?rio predom?nio da fenacetina como adulterante. O teor de coca?na das amostras estudadas apresentou varia??o dentro de um amplo intervalo (0-93%). Os teores m?dios de coca?na observados para as formas de p? e de crack foram, respectivamente, 31,7% e 54,3%, sendo tais valores estatisticamente distintos. A vigil?ncia em rela??o ?s caracter?sticas de drogas il?citas deve ser uma atividade cont?nua para fornecer aos ?rg?os de controle e de sa?de p?blica elementos de aux?lio ?s atividades de repress?o e tamb?m para tomadas de decis?o e de diagn?stico por parte dos profissionais de sa?de que lidam com atendimento aos usu?rios de drogas. As informa??es obtidas neste trabalho poder?o contribuir para futuras a??es de educa??o e conscientiza??o em rela??o aos riscos associados ao uso de drogas. / Disserta??o (Mestrado Profissional) ? Programa de P?s-Gradua??o em Sa?de, Sociedade e Ambiente, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / Brazil is among the countries with the highest cocaine use in the world. The issues related to cocaine use raise concerns, since they are accompanied by consequences that affect the modern society multiple dimensions. The problems associated with illicit trafficking and drug abuse are widespread throughout the country, reaching small towns. The adulterants presence can cause unexpected reactions as well as potentiate the damages to the users? health. This study aimed to characterize the cocaine samples seized in Diamantina, Minas Gerais, Brazil, regarding the cocaine content and the adulterants presence. In the study?s first phase, an analytical methodology was validated for the cocaine quantification in samples seized using Gas Chromatography coupled to a Mass Spectrometry with Selected-Ion Monitoring (GC-MS-SIM). In a second phase, one hundred and twenty-nine samples were analyzed, from which sixty-seven were seized as powder and sixty-two as crack. Analyzes were performed to identify adulterants and to determine the cocaine content in the samples. The identification of adulterants were carried out by a Gas Chromatography coupled to a Mass Spectrometry (GC-MS) in the full scan mode, and quantification of cocaine contend by GC-MS-SIM. The mean content comparison between the samples seized as powder and crack was performed by the Mann-Whitney U test. Phenacetin was the main adulterant found. Other adulterants such as benzocaine, caffeine, levamisole, lidocaine and procaine were also detected. The samples seized as crack showed a predominance of phenacetin as adulterant. The cocaine content of the samples studied varied within a wide range (0-93%). The average cocaine contents observed for the powder and crack forms were, respectively, 31,7% and 54,3%, and these values were statistically different. The surveillance in relation to the illicit drugs characteristics should be a continuous activity to provide control to the public health agencies with support elements for repression activities, as well as decision-making and diagnosis by the health professionals dealing with the drug users? care. The information obtained in this study may contribute to the future education and awareness actions regarding the risks associated with the drug use.

The regulations of many food products in the United States have been made and followed very well but unfortunately some products are not put under such rigorous standards as others. This leads to products being sold, that are thought to be healthy, but in reality contain unknown ingredients that may be hazardous to the consumers. With the use of several instrumentations and techniques the detection, characterization and identification of these unknown contaminates can be determined. Both the AZ-100 and the TE2000 inverted microscope were used for visual characterizations, image collection and to help guide the extraction. Direct analyte-probed nanoextraction (DAPNe) technique and nanospray ionization mass spectrometry (NSI-MS) was the technique used for examination and identification of all adulterants. A Raman imaging technique was than introduced and has proven to be a rapid, non-destructive and distinctive way to localize a specific adulterant. By compiling these techniques then applying them to the FDA supplied test samples three major adulterants were detected and identified.

The popularity of herbal medicines as adjuncts in the treatment of diabetes mellitus, has increased in recent years. However, recent studies have demonstrated the presence of synthetic drugs, as adulterants, in these formulations, what can cause serious problems to the health of the patient, since interactions and pharmacological effects are unpredictable. This work describes the development of a method for the simultaneous determination of metformin, glibenclamide, gliclazide and chlorpropamide employing capillary zone electrophoresis (CZE) with contactless conductivity detection (C4D). The work was carried out using a capillary electrophoresis system built in the laboratory. The optimized conditions for the determination of adulterants in herbal medicines by CZE-C4D were the following: 20 mmol L-1 sodium acetate at pH 10.0 as working electrolyte, separation potential of -15kV, separation temperature of 25ºC, indirect conductivity detection operating at 400 kHz and amplitude wave of 2 Vpp, hydrodynamic injection by gravity (20 cm left side elevation for 60 s). The method was validated and applied to the determination of hypoglycemics in pharmaceutical formulations commercialized by compounding pharmacies in Brazil. The method allows the identification of adulterants and its quantification from 0.24 mg to metformin, 0.15 mg to glibenclamide, 0.33 mg to gliclazide and 0.24 mg to chlorpropamide. / A popularidade dos fitoterápicos como coadjuvantes no tratamento do diabetes mellitus, tem aumentado nos últimos anos. No entanto, trabalhos recentes têm demonstrado a presença de fármacos sintéticos, como adulterantes, nestas formulações, o que pode causar sérios problemas à saúde do paciente, uma vez que interações e efeitos farmacológicos são imprevisíveis. Este trabalho descreve o desenvolvimento de um método para a determinação simultânea de metformina, glibenclamida, gliclazida e clorpropamida, empregando eletroforese capilar de zona (CZE) com detecção condutométrica sem contato (C4D), usando um sistema de eletroforese capilar construído em laboratório. As condições otimizadas para a determinação de adulterantes em fitoterápicos por CZE-C4D foram: eletrólito de trabalho acetato de sódio 20 mmol L-1 (pH 10,0); potencial de separação - 15 kV; temperatura de 25ºC; detecção indireta operando em 400kHz e amplitude de onda de 2vpp; e injeção por gravidade de 20 cm por 60 s. O método foi validado e aplicado para a avaliação de hipoglicemiantes em formulações herbáreas comercializadas por farmácias no mercado brasileiro. O método permite a identificação dos adulterantes e sua quantificação a partir de 0,24 mg para a metformina, 0,15 mg para a glibenclamida, 0,33 mg para a gliclazida e 0,24 mg para a clorpropamida.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The adulteration of phytotherapeutic formulations used for weight loss with synthetic pharmaceuticals has been increasing in recent years. The cases of adulteration have been reported in the literature, showing that there is a great concern about this problem, which involves the development of analytical methodologies able to detect them. This paper describes the development of a method for the simultaneous determination of amfepramone, fenproporex, sibutramine and fluoxetine by using capillary zone electrophoresis (CZE) with capacitively coupled contactless conductivity detection (C4D) in a homemade capillary electrophoretic system. The optimized conditions for separation of the pharmaceuticals by CZE-C4D were the following: 50 mmol L-1 phosphate buffer (pH 5.0) containing acetonitrile 50% (v/v) as working electrolyte, separation potential of -15 kV, separation temperature of 25 °C, hydrodynamic injection by gravity (20 cm left side elevation for 60 s). The C4D detection was performed by using a homemade detector, which employs a sinusoidal wave generator operating at 600 kHz frequency and 2 Vpp wave amplitude. The CZE-C4D method was validated for the determination of amfepramone, fenproporex, sibutramine and fluoxetine and it was applied to the analysis of phytotherapeutic formulations used for weight loss, which have been purchased in different commercial pharmacies in the city of Santa Maria. This method was fit in the analysis of four synthetic drugs studied, with a wide linear response range (10 to 500 mg L-1), low detection limits (4 to 5 mg L-1), precision (6 to 9 %) and accuracy (95 to 112 %) . The recovery experiments were carried out in the samples and the recovery values ranged between 80 and 120 % for all the studied samples. The developed method showed high sensitivity, selectivity and analytical precision and it can be used for determining these substances as contaminants in herbal natural formulations. It also an important alternative to the federal control agencies due to its simplicity, rapidity and low cost of analysis considering the small quantities of reagents and samples used. / A adulteração de formulações fitoterápicas emagrecedoras com fármacos sintéticos tem aumentado muito nos últimos anos. Os casos de adulteração têm sido relatados na literatura, comprovando que existe uma maior preocupação com relação a este problema, o que implica no desenvolvimento de metodologias analíticas capazes de detectá-los. Este trabalho descreve o desenvolvimento de um método para a determinação simultânea de anfepramona, femproporex, sibutramina e fluoxetina empregando eletroforese capilar de zona (CZE) com detecção condutométrica sem contato capacitivamente acoplada (C4D), usando um sistema de eletroforese capilar construído em laboratório. As condições otimizadas para a separação dos fármacos por CZE-C4D foram as seguintes: eletrólito de trabalho tampão fosfato (pH 5,0) 50 mmol.L-1 contendo acetonitrila 50% (v/v), potencial de separação -15 kV, temperatura de separação 25 °C, injeção hidrodinâmica por gravidade com altura de injeção de 20 cm durante 60 s. A detecção por C4D foi realizada usando um detector construído em laboratório, que emprega um gerador de onda senoidal operando a uma freqüência de 600 kHz e amplitude de onda de 2 Vpp. O método de CZE-C4D foi validado para a determinação de anfepramona, femproporex, sibutramina e fluoxetina e empregado na análise de formulações fitoterápicas emagrecedoras adquiridas em diferentes farmácias de manipulação na cidade de Santa Maria. Este método mostrou-se adequado na análise dos quatro fármacos sintéticos estudados, apresentando uma ampla faixa linear de trabalho (10 a 500 mg L-1), baixos limites de detecção (4 a 5 mg L-1), precisão (6 a 9%) e exatidão (95 a 112%). Os ensaios de recuperação realizados promoveram recuperações entre 80 e 120% para os fármacos sintéticos estudados. O método desenvolvido apresentou alta sensibilidade, seletividade e precisão analítica, podendo ser empregado na determinação destas substâncias como adulterantes em formulações fitoterápicas, tornando-se uma alternativa para órgãos fiscalizadores devido a sua simplicidade, rapidez e baixo custo de análise devido às quantidades reduzidas de reagentes e amostras utilizadas.