Thesis (Ph. D.)--Ohio State University, 2007. / Full text release at OhioLINK's ETD Center delayed at author's request

Thesis (M.S.)--Oregon State University, 2009. / Printout. Includes bibliographical references (leaves 47-51). Also available on the World Wide Web.

Drugs of Abuse (DOAs) are among the single largest contributor to crime in the United States and present a high cost to society in terms of financial costs and physical/mental well-being of individuals. The forensic community requires a variety of validated methods to detect and analyze DOAs in a variety of different sample types, and most developed methods utilize a liquid or gas chromatography (GC or LC) separation system paired to a mass spectrometer (MS) detection detector. Capillary Electrophoresis (CE) based separation techniques have also been experimented with due to this technique’s high efficiency and speed, high resolving power, low sample consumption, and potentially lower cost when compared to GC or LC based techniques, even though the sensitivity of these systems is perceived to be weaker. The goal of this research to develop a CE-MS/MS method utilizing the ZipChipTM to demonstrate it can accurately and reliably detect and quantify DOAs. The DOAs analyzed for this method were opioids and benzodiazepines, and these were 6-monacetylmorphine, 7-aminoclonazepam, codeine, diazepam, dihydrocodeine, 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine fentanyl, heroin, hydrocodone, hydromorphone, meperidine, methadone, morphine, norfentanyl, oxycodone, and oxymorphone. Standard Practices for Method Validation in Forensic Toxicology guidelines from the Academy Standards Board (ASB) of Toxicology were used as the template for this validation; samples were prepared and analyzed as neat standards in diluent, blood and urine were assessed for interferences, ionization suppression/enhancement, and extraction recovery. The total runtime for the method was 3.5 minutes, with the retention time range being 1.4 to 2.9 minutes. All samples were prepared using compound standards diluted in metabolite diluent, which consisted of methanol, ammonium acetate, and water prior to injection. The calibration curves consisted of eight calibrator samples that ranged from 0.5 ng/ml to 200 ng/ml for all analytes, and a linear model was used for each compound. The minimum acceptable 𝑅2 value was set to >0.98, and each curve had a weighing factor of 1𝑥2. Each curve for most of the compounds achieved the minimum requirement apart from two Codeine curves (0.9781 and 0.9785) and 7-aminoclonazepam (0.9791). Bias and precision were assessed at three concentrations- 5, 100, and 150 ng/ml. The minimum requirement for bias and precision for a compound was if the percent bias or coefficient of variation was within +/- 20%. Most compounds in this method exhibit acceptable levels of bias (except for Dihydrocodeine which had a bias of 24.58% at 100 ng/ml), and the only compounds to meet the minimum requirement for precision were 6-MAM, 7-aminoclonazepam, diazepam, fentanyl, methadone, and morphine. The limit of detection and limit of quantitation were both set at the lowest calibrator level of 0.5 ng/ml, and no carryover was observed in this method. No interferences occurred due to both deuterated internal standards and from common compounds such as benzylecogine, cocaine, and lidocaine, but blood cause signal interference with fentanyl and urine caused signal interference with methadone and norfentanyl. Ionization suppression and enhancement was observed for a majority of the compounds, and this observation will need to be assessed as to the effect it has on validation parameters in the future. The results collected suggest that accurate, reliable, and sensitive data may be collected if a compound has a specifically paired deuterated internal standard included in the sample. The speed of the suggested method and the minimal sample preparation could be desirable for forensic use. Further testing will need to be conducted to fully validate this method for blood and urine.

The opioid epidemic has become a serious public health problem in the United States. The increasing abuse of synthetic opioids has raised concerns in the society. Fentanyl is a synthetic opioid analgesic which has resulted in an increasing number of drug overdoses since 2013. In addition, fentanyl analogs, originally manufactured for use as analgesics or animal tranquilizers, have emerged in the United States drug market. Fentanyl and its analogs, similar to other opioids, work as full µ-agonists, binding with µ-receptors in the brain. Fentanyl and its analogs elicit more potent effects compared to the traditional opioids being abused such as morphine or heroin. With the emergence of fentanyl analogs in the drug market, identifying and differentiating those analogs becomes a challenge due to their structural similarities to fentanyl. The purpose of this research was to develop a method of identifying and quantifying nine fentanyl analogs in urine and oral fluid using the QSight® Triple Quad LC-MS/MS, coupled with a Halo® C18, 2.7µm column. The method was validated based on AAFS Standards Board (ASB) Standard 036, Standard Practices for Method Validation in Forensic Toxicology. The analytes in this research included fentanyl, norfentanyl, acetyl fentanyl, carfentanil, cyclopropyl fentanyl, methoxyacetyl fentanyl, valeryl fentanyl, furanyl fentanyl and 4-anilino-N-phenethylpiperdine (4ANPP). All samples, calibrators, and quality controls (QC) were prepared by spiking certified reference standards into donated human urine or human oral fluid. Supported liquid extraction (SLE) was performed as the sample preparation method using ISOLUTE® SLE+ 1mL columns followed by evaporation. All samples were reconstituted with 200 µL methanol. The mobile phases used in this method were 5mM ammonium formate in Millipore water with 0.1% formic acid and methanol with 0.1% formic acid. A 10-minute LC method achieved complete resolution of the analytes, with specific retention times ranging from 3.5 to 5.7 minutes. For urine and oral fluid analysis, the calibration range for all analytes was established from 1 to 70 ng/mL. The resulting r2 values were greater than 0.988 for all analytes. Bias and precision were evaluated at 3, 25 and 60 ng/mL, and bias and percent coefficient of variation (%CV) for within and between run precision had acceptable values within ±20%. The limit of detection (LOD) was 0.1 ng/mL for most fentanyl analogs, with a LOD of 0.01 ng/mL for valeryl fentanyl and furanyl fentanyl. Carryover was not detected for any analytes in either matrix. Recovery of all compounds following SLE for both urine and oral fluid was above 50%. For urine, the ion enhancement and suppression of all analytes was within 25%. For oral fluid, the ion enhancement and suppression of most analytes was within 25% except valeryl fentanyl, which experienced suppression of 35%. The matrices analyzed had no interference effect on the detection or quantitation of analytes in this method. The interference effects of different commonly encountered drugs were studied and showed minimal impacts on the results generated from this method. All analytes were stable for up to 72 hours at room temperature, except cyclopropyl fentanyl. In conclusion, using the QSight® Triple Quad LC-MS/MS following SLE effectively identified and quantified fentanyl analogs present in both urine and oral fluid. This method has shown its potential to be applied to casework samples for fentanyl analogs detection.

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O relevante conceito de sustentabilidade dos dias atuais leva a população a pensar no tratamento dos recursos naturais e principalmente na qualidade e escassez da água. A grave problemática quanto à gestão dos resíduos urbanos no país, desde sua produção, coleta e disposição final são os desafios colocado aos municípios e a sociedade em geral. O uso cada vez mais abundante dos medicamentos farmacêuticos gera uma demanda de resíduos que acabam atingindo os leitos dos rios. Com avanço das tecnologias é possível monitorar e conhecer os resíduos que afetam indiretamente e diretamente as águas das bacias hidrográficas. O objetivo deste trabalho foi desenvolver e validar uma metodologia analítica para a determinação dos resíduos de fármacos (ácido acetil salicílico, diclorofenaco de sódio, paracetamol, ibuprofeno e fenoprofeno) em águas utilizando a cromatografia líquida de ultra performance acoplada à espectrometria de massas tipo tandem (UPLC-MS/MS). Foram utilizadas duas fases moveis distintas. Para os fármacos paracetamol e diclofenaco foi utilizado como fase móvel água: metanol (1:1; V/V) com adição de ácido fórmico e a ionização de eletrospray em modo positivo; para os fármacos acetil salicílico, ibuprofeno e fenoprofeno foi utilizado água: metanol (1:1; v/v) com adição de acetato de amônio e a ionização de eletrospray em modo negativo. O desempenho do método foi avaliado quanto aos seguintes parâmetros: especificidade e seletividade, faixa de trabalho, linearidade; limite de detecção e limite de quantificação, exatidão, robustez e incerteza de medição. Os resultados obtidos comprovaram a adequabilidade do método ao propósito supracitado. Os valores obtidos para o limite de decisão (ccα) e capabilidade de detecção (ccβ) foram: paracetamol 0,21 e 0,34 μg L -1; diclofenaco 2,42 e 3,24 μg L -1 ; AAS 1,56 e 2,45 μg L -1; ibuprofeno 2,34 e 3,21 μg L -1 e fenoprofeno 1,89 e 2,33 μg L-1, respectivamente. A metodologia foi aplicada na caracterização de amostras de água superficial (bruta) e tratada proveniente de áreas de captação e de tratamento de água da bacia hidrográfica do Paraíba do Sul. Foram realizadas duas coletas distintas, setembro/ 2010 e novembro/ 2010, nos municípios de Guararema, São José dos Campos, Taubaté e Pindamonhangaba. Em 31,2 % das amostras, Cinco amostras de água bruta das 16 amostras analisadas, foram encontrados resíduos de paracetamol. Os resultados obtidos apresentaram-se em uma faixa de concentração de 0,10 a 0,50 μg L -1. / The relevant concept of sustainability of the present day leads people to think about the treatment of natural resources and particularly in the quanlity and scarcity of water. The serious problems regarding the management of municipal waste in the country, from production, collection and disposal are the challenges facing municipalities and society in general. The increasing use of pharmaceutical drugs most abundant generates a demand for waste that eventually reach the river beds. With advancement of technologies and know you can monitor the waste that directly and indirectly affect the waters of river basins. The objective of this study was to develop and validade analytical methods for residues of drugs (aspirin, sodium diclofenac, paracetamol, ibuprofen and fenoprofen) in water using ultra performance liquida chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). We used two different mobile phases. For the drugs paracetamol and diclofenac was used as mobile phase water:methanol (1:1, v/v) with addition of formic acid in positive electrospray ionization mode. For drugs acetyl salicylic acid, ibuprofen and fenoprofen was used mobile phase water:methanol (1:1, v/v) with addition of ammonium acetate and negative electrospray ionization mode. The performance of the method was evaluated on the following parameters: specificity and selectivity, working range, lineariry, limit of detection and limit of quantification, accuracy, ruggedness and uncertainty measurement. The result obtained proved the suitability of the method for fit purpose. The values obtained for the decision limit (ccα) and detection capability (ccβ) were 0.21 and 0.34 μg L-1, diclofenac 2.42 and 3.24 μgL-1, ASA 1.56 and 2.45 μgL-1, respectively. The methodology was applied in the characterization of samples of surface water (raw) and treated from catchment areas and water treatment basin of Paraíba do sul were two distinct collections, September/2011 and November 2010 in the municipalities of Guararema, São José dos Campos, Taubaté and Pindamonhangaba. In 32,2% of all samples, five samples of 16 raw water samples, residues were found for paracetamol. The results were presented in a concentration range from 0.10 to 0.50 μg L-1.

O relevante conceito de sustentabilidade dos dias atuais leva a população a pensar no tratamento dos recursos naturais e principalmente na qualidade e escassez da água. A grave problemática quanto à gestão dos resíduos urbanos no país, desde sua produção, coleta e disposição final são os desafios colocado aos municípios e a sociedade em geral. O uso cada vez mais abundante dos medicamentos farmacêuticos gera uma demanda de resíduos que acabam atingindo os leitos dos rios. Com avanço das tecnologias é possível monitorar e conhecer os resíduos que afetam indiretamente e diretamente as águas das bacias hidrográficas. O objetivo deste trabalho foi desenvolver e validar uma metodologia analítica para a determinação dos resíduos de fármacos (ácido acetil salicílico, diclorofenaco de sódio, paracetamol, ibuprofeno e fenoprofeno) em águas utilizando a cromatografia líquida de ultra performance acoplada à espectrometria de massas tipo tandem (UPLC-MS/MS). Foram utilizadas duas fases moveis distintas. Para os fármacos paracetamol e diclofenaco foi utilizado como fase móvel água: metanol (1:1; V/V) com adição de ácido fórmico e a ionização de eletrospray em modo positivo; para os fármacos acetil salicílico, ibuprofeno e fenoprofeno foi utilizado água: metanol (1:1; v/v) com adição de acetato de amônio e a ionização de eletrospray em modo negativo. O desempenho do método foi avaliado quanto aos seguintes parâmetros: especificidade e seletividade, faixa de trabalho, linearidade; limite de detecção e limite de quantificação, exatidão, robustez e incerteza de medição. Os resultados obtidos comprovaram a adequabilidade do método ao propósito supracitado. Os valores obtidos para o limite de decisão (ccα) e capabilidade de detecção (ccβ) foram: paracetamol 0,21 e 0,34 μg L -1; diclofenaco 2,42 e 3,24 μg L -1 ; AAS 1,56 e 2,45 μg L -1; ibuprofeno 2,34 e 3,21 μg L -1 e fenoprofeno 1,89 e 2,33 μg L-1, respectivamente. A metodologia foi aplicada na caracterização de amostras de água superficial (bruta) e tratada proveniente de áreas de captação e de tratamento de água da bacia hidrográfica do Paraíba do Sul. Foram realizadas duas coletas distintas, setembro/ 2010 e novembro/ 2010, nos municípios de Guararema, São José dos Campos, Taubaté e Pindamonhangaba. Em 31,2 % das amostras, Cinco amostras de água bruta das 16 amostras analisadas, foram encontrados resíduos de paracetamol. Os resultados obtidos apresentaram-se em uma faixa de concentração de 0,10 a 0,50 μg L -1. / The relevant concept of sustainability of the present day leads people to think about the treatment of natural resources and particularly in the quanlity and scarcity of water. The serious problems regarding the management of municipal waste in the country, from production, collection and disposal are the challenges facing municipalities and society in general. The increasing use of pharmaceutical drugs most abundant generates a demand for waste that eventually reach the river beds. With advancement of technologies and know you can monitor the waste that directly and indirectly affect the waters of river basins. The objective of this study was to develop and validade analytical methods for residues of drugs (aspirin, sodium diclofenac, paracetamol, ibuprofen and fenoprofen) in water using ultra performance liquida chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). We used two different mobile phases. For the drugs paracetamol and diclofenac was used as mobile phase water:methanol (1:1, v/v) with addition of formic acid in positive electrospray ionization mode. For drugs acetyl salicylic acid, ibuprofen and fenoprofen was used mobile phase water:methanol (1:1, v/v) with addition of ammonium acetate and negative electrospray ionization mode. The performance of the method was evaluated on the following parameters: specificity and selectivity, working range, lineariry, limit of detection and limit of quantification, accuracy, ruggedness and uncertainty measurement. The result obtained proved the suitability of the method for fit purpose. The values obtained for the decision limit (ccα) and detection capability (ccβ) were 0.21 and 0.34 μg L-1, diclofenac 2.42 and 3.24 μgL-1, ASA 1.56 and 2.45 μgL-1, respectively. The methodology was applied in the characterization of samples of surface water (raw) and treated from catchment areas and water treatment basin of Paraíba do sul were two distinct collections, September/2011 and November 2010 in the municipalities of Guararema, São José dos Campos, Taubaté and Pindamonhangaba. In 32,2% of all samples, five samples of 16 raw water samples, residues were found for paracetamol. The results were presented in a concentration range from 0.10 to 0.50 μg L-1.

Orientador: Marcelo Alexandre Prado / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-21T09:52:53Z (GMT). No. of bitstreams: 1 MirandaeSilva_LigiaMaria_M.pdf: 148256 bytes, checksum: 789cac2002bb2e8dcb1bf70832d395b6 (MD5) Previous issue date: 2012 / Resumo: O crescente aumento populacional em escala mundial, tornou necessário um grande esforço por parte da agricultura para aumentar, a cada ano, a produção de alimentos para atender as necessidades do mercado externo e interno do Brasil. Recursos técnicos e científicos passaram então, a serem aplicados em busca da melhoria na produção dos cultivos,principalmente mediante o uso de fertilizantes e praguicidas. Com isso, a sociedade se deparou com problemas de ordem de equilíbrio ambiental e saúde pública, pois devido à contínua diversificação dos fitoparasitas, surgem, a todo momento, reduções do período de tempo entre aplicações consecutivas, e mais importante talvez, usos de doses mais altas e emprego simultâneo de diferentes pesticidas, por parte dos agricultores, objetivando complementar ações específicas ou alcançar efeitos sinérgicos para maiores rendimentos na produção. Tal situação traz como conseqüência óbvia e direta, o aumento, inaceitável, dos riscos de contaminação do meio ambiente com resíduos químicos de defensívos da área agropecuarista prejudiciais à saúde, o que leva a inúmeros problemas relativos à segurança alimentar dos produtos consumidos, e à uma preocupação de âmbito nacional evidenciada pela criação do Programa de Análise de Resíduos de Agrotóxicos em alimentos (PARA) da ANVISA. O aumento na necessidade de detecção e quantificação destes compostos, acarretou o desenvolvimento de pesquisas no setor, a fim de atingir uma melhoria na eficiência,qualidade e rapidez de resposta nas análises. A possibilidade do estudo de não apenas um de cada vez, mas de até 300 compostos sendo extraídos, detectados e quantificados simultâneamente se tornou a saída mais viável, tanto qualitativa quanto economicamente, facilitando o monitoramento contínuo do fornecimento de produtos do setor alimentício pelos chamados métodos multiresíduos. O presentre trabalho teve como princípio a validação de um método multiresíduo para análise de 14 analitos usando uma técnica de alto poder de concentração e limpeza do extrato como o GPC (Gel Permeation Chromatography) e detecção e quantificação por GC-MS/MS e LC-MS/MS. Os pesticidas investigados englobam classes como: acaricidas, inseticidas, fungicidas, nematicidas e formicidas de aplicação foliar, em sementes ou em solo, sendo que o acefato, metamidofós, acetamiprido e o thiamethoxan foram extraídos de amostras de batata e feijão e analisados por LC-MS/MS e a azoxistrobina, bifentrina, carbofuran, chlorotalonil, clorpirifós, clorfenapir, etofenprox, famoxadone,metalaxil, procimidone e o tebuconazole em amostras de batata e tomate e analisados por GCMS/MS. Os limites de detecção (LD) encontrados variaram de 0,06 a 2,89µg/L, e os coeficientes de variação (CV), de 0,036 a 2,036%. As recuperações foram determinadas em cada tipo de amostras, e os valores encontrados estavam entre 93,34% e 109,67%. Nenhuma das matrizes utilizadas apresentaram resultados insatisfatórios e o método utilizado mostrouse robusto e de fácil aplicação para todos os analitos testados / Abstract: The growing population worldwide, has required a great effort on the part of agriculture to increase each year, the production of food to meet the needs of external and internal market of Brazil. Technical and scientific resources spent then, to be applied in pursuit of improved crop production, mainly through the use of fertilizers and pesticides.With this, the company encountered problems in the balance of environmental and public health, since due to the continuous diversification of plant parasites, arise at any moment,reductions in the time period between consecutive applications, and perhaps most important,uses more doses high and simultaneous use of different pesticides by farmers, aiming to complete specific actions or to achieve synergistic effects in producing higher yields. This situation brings obvious and direct consequence, the increase unacceptable risk of environmental contamination with chemical residues from pesticides in farms are harmful to health, which leads to numerous problems relating to food safety of the products consumed, and to a concern nationwide evidenced by the creation of the Program Analysis of Pesticide Residues in Food (TO) of ANVISA. The increase in the necessity for detection and quantification of these compounds, led the development of research in the sector in order to achieve an improvement in efficiency, quality and responsiveness in the analyzes. The possibility of studying not just one at a time, but up to 300 compounds being extracted,detected and quantified simultaneously output became more viable, both qualitatively and economically, facilitating continuous monitoring of the supply of products by the food industry called methods multiresidue. The principle presentre work was the validation of a multiresidue method for analysis of 14 analytes using a technique of high power concentration and cleanup of the extract as GPC (Gel Permeation Chromatography) and detection and quantification by GC-MS/MS and LC- MS / MS. The pesticides investigated include classes such as acaricides, insecticides, fungicides, insecticides and nematicides foliar, seed or soil,and acephate, methamidophos, and Acetamiprid thiamethoxan were extracted from samples of potatoes and beans and analyzed by LC-MS / MS and azoxystrobin, bifenthrin, carbofuran,chlorothalonil, chlorpyrifos, chlorfenapyr, etofenprox, famoxadone, metalaxyl, procymidone and tebuconazole in samples of potato and tomato and analyzed by GC-MS/MS. The limits of detection (LOD) ranged from 0.06 to 2.89 mg / L, and the coefficients of variation (CV), 0.036 to 2.036%. The recoveries were determined for each type of samples, and the values were between 93.34% and 109.67%. None of the arrays used had unsatisfactory results and method proved to be robust and easy to apply for all analytes tested / Mestrado / Ciência de Alimentos / Mestra em Ciência de Alimentos