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Christian Fernandeshttp://lattes.cnpq.br/2204207812156880Clésia Cristina NascentesFernanda Costa PinheiroLetícia Malta CostaLuan Farinelli Dinizhttp://lattes.cnpq.br/9236185761249311Julia Facci Colangelo2023-10-30T17:28:28Z2023-10-30T17:28:28Z2023-09-01http://hdl.handle.net/1843/60250A falsificação de medicamentos é uma atividade ilegal em crescimento no mundo. Os principais alvos deste crime são os medicamentos de alto custo e os mais procurados pela população, particularmente aqueles destinados à impotência sexual contendo sildenafila e tadalafila. A determinação elementar em produtos farmacêuticos é um assunto que está em destaque devido às mudanças regulatórias e das técnicas analíticas empregadas para o monitoramento destas impurezas, e, sobretudo, devido à toxicidade de alguns elementos. A espectrometria de massas com plasma acoplado indutivamente (ICP-MS) é a técnica de maior detectabilidade para análise elementar. Diante disto, neste trabalho foram analisadas seis amostras autênticas e dez amostras apreendidas pela Polícia Federal e pela Polícia Civil do Estado de Minas Gerais de comprimidos contendo sildenafila e tadalafila, de acordo com os capítulos 232 e 233 da Farmacopeia Americana (USP). O objetivo foi estabelecer uma comparação entre os teores das impurezas elementares determinadas nas amostras autênticas e apreendidas. Para isso, um novo método utilizando digestão ácida em forno de micro-ondas e ICP-MS foi desenvolvido e validado visando a determinação simultânea dos elementos Ag, As, Au, Ba, Cd, Co, Cr, Cu, Hg, Ir, Li, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru, Sb, Se, Sn, Tl e V. O procedimento de preparo de amostras foi otimizado por meio de planejamento fatorial completo 22 com ponto central, avaliando-se a concentração da água régia invertida e o volume de H2O2. Nas condições ótimas, 0,1 g das amostras foram submetidas à digestão em forno assistido por radiação micro-ondas usando 5 mL de 3HNO3:1HCl 20% v v-1 e 2 mL de H2O2 30% v v-1. A precisão e a exatidão foram avaliadas em três níveis (0,5; 1,0 e 5,0 μg L-1) em duas amostras autênticas. As recuperações obtidas variaram entre 70 e 127%, com exceção de Ag, Cu e Ni. Os limites de quantificação foram calculados a partir de 10 brancos independentes e variaram entre 0,005 (Tl) e 1,3 μg g-1 (Se). Os teores determinados variaram de 0,006 (Cd) a 6,0 μg g-1 (Ni), sendo que as maiores concentrações foram determinadas nas amostras apreendidas. Os teores determinados nas amostras autênticas e apreendidas estavam abaixo dos seus respectivos limites máximos permitidos, porém os resultados obtidos demonstram o risco ao qual a população está submetida quando utiliza medicamentos falsificados.Drug counterfeiting is an illegal activity in expansion worldwide. In this regard, the main targets are those medicines with high costs, or the ones sought after by the population, among which stand out those intended for sexual impotence, particularly drugs containing sildenafil and tadalafil. Elemental impurities determination in pharmaceuticals has become an emerging topic due to the regulatory changes about the permissible limits, the analytical techniques applied for this determination and also because of the toxicity of some elements even at trace levels. The inductively coupled plasma mass spectrometry (ICP-MS) is the technique that presents the highest sensitivity for elemental impurities analysis. Based on the above considerations, in this study six authentic samples and ten samples seized by the Federal Police and the Civil Police of the state of Minas Gerais of tablets containing sildenafil and tadalafil were analyzed in accordance with chapter 232 and 233 of the United States Pharmacopeia (USP). The main goal of this study was to establish a comparison between the levels of elemental impurities determined in the authentic and seized samples. For this, a new method using a microwave assisted acid digestion and ICP-MS was developed and validated aiming at the simultaneous determination of the elements Ag, As, Au, Ba, Cd, Co, Cr, Cu, Hg, Ir, Li, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru, Sb, Se, Sn, Tl e V. The sample preparation procedure was optimized through a 22 factorial design with central point, evaluating the reverse aqua regia concentration and the volume of H2O2. In optimal conditions 0.1 g of the samples were submitted to a microwave-assisted digestion using 5 mL of 3HNO3:1HCl 20% v v-1 and 2 mL de H2O2 30% v v-1. The precision and accuracy were evaluated by addition and recovery experiments at three levels (0.5; 1.0 e 5.0 µg L-1) in two authentic samples. Recoveries ranged from 70 to 127% except for Ag, Cu and Ni. The limits of quantification were calculated from 10 independent blanks and ranged from 0.005 (Tl) to 1.3 µg g-1 (Se). The levels determined ranged from 0.006 (Cd) to 6.0 µg g-1 (Ni) and the highest concentrations were determined in the seized samples. The levels determined in authentic and seized samples are below their respective maximum allowable limits, as established in chapter 232 of USP, although, this study shows the risk people are submitted when exposed to counterfeit drug products.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Ciências FarmacêuticasUFMGBrasilFARMACIA - FACULDADE DE FARMACIAhttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessControle de qualidade de medicamentosAnálise elementarSildenafilaTadalafilaICP-MSDeterminação de impurezas elementares em amostras autênticas e apreendidas de comprimidos contendo sildenafila e tadalafila.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALDissertação - Julia Facci Colangelo.pdfDissertação - Julia Facci Colangelo.pdfapplication/pdf2780573https://repositorio.ufmg.br/bitstream/1843/60250/1/Disserta%c3%a7%c3%a3o%20-%20Julia%20Facci%20Colangelo.pdff048567dcd67629f0fb2eedbef642438MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufmg.br/bitstream/1843/60250/2/license_rdfcfd6801dba008cb6adbd9838b81582abMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/60250/3/license.txtcda590c95a0b51b4d15f60c9642ca272MD531843/602502023-10-30 14:28:29.202oai:repositorio.ufmg.br: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ório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-10-30T17:28:29Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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