Impurezas inorgânicas em medicamentos: do preparo de amostra a determinação elementar por ICP-MS
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Data
2016-11-30
Autores
Coelho, Jéssica Silva [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O Brasil possui um mercado farmacêutico promissor e em crescimento, promovendo uma busca por medicamentos de alta qualidade. Órgãos como a Agência Nacional de Vigilância Sanitária (ANVISA) no Brasil, a Farmacopeia Norte Americana (USP), a Administração de Alimentos e Medicamentos (FDA) e a Agência de Medicina Europeia (EMA) no âmbito internacional descrevem legislações para garantir a qualidade dos medicamentos, além do controle e monitoramento de contaminantes, principalmente elementos potencialmente tóxicos. O principal objetivo do trabalho foi o desenvolvimento e otimização de métodos de preparo de amostras aplicado a medicamentos e seus insumos visando a determinação de impurezas inorgânicas por Espectrometria de Massas Acoplada ao Plasma Induzido (ICP-MS). Foram estudadas amostras de Aciclovir pomada e seus excipientes e de comprimidos de Omeprazol genérico e similar. Um método de digestão ácida assistida por radiação micro-ondas (MW-AD) foi otimizado por planejamento fatorial para amostras de Aciclovir e sua eficiência foi avaliada pela análise dos teores de carbono residual (RCC). Para avaliação da exatidão do método foram avaliadas as recuperações dos elementos adicionados às amostras antes da MW-AD ficando entre 95,1 e 126%, e após a etapa de digestão onde a variação foi na faixa 85,6 a 132%, com exceção do Cr. Os limites de detecção (LD) obtidos foram em ng L-1 na faixa de 0,2 para 75As+ e de 91 para 58Ni+. As determinações de 75As+, 65Cu+, 52Cr+, 58Ni+, 208Pb+, e 51V+ variaram de 2,3 ± 0,8 para 75As+ até 3446 ± 47 para 52Cr+ em µg kg-1. As amostras de Omeprazol genérico e similar foram decompostas em dois programas de aquecimento na MW-AD e suas eficiências de digestão avaliada para estas matrizes. As recuperações de As, Cd, Hg e Pb foram de 75,6 a 130,0% nestas amostras. Os LD’s foram menores que 0,07 ng L-1. As determinações de 75As+ e 208Pb+ variaram de 0,013 a 0,171 µg g-1 e 0,134 e 0,154 µg g-1, respectivamente; 202Hg+ e 111Cd+ estão abaixo dos LD para ambos os métodos. O desenvolvimento de um método de extração ácida assistida por ultrassom (UAE) aplicado às amostras de omeprazol foi avaliado através de um planejamento fatorial e indicou ser uma alternativa promissora que emprega menores volumes de reagentes, menor tempo de extração, maior frequência analítica, sendo um método limpo colaborando para o desenvolvimento da química verde gerando desta forma menores volumes de resíduos químicos.
Brazil has a promising and growing pharmaceutical market promoting a search for high quality medicines. Agencies such as the Brazilian Health Surveillance Agency (ANVISA) in Brazil, the United States Pharmacopeia (USP) and Food and Drug Administration (FDA) and the European Medicine Agency (EMA) in the international scope describe legislation to ensure the quality of medicines in addition to control and monitoring of inorganic contaminants, especially potentially toxic inorganic elements. The main objective were the development and optimization of sample preparation methodologies applied to medicines and their manufacture products in order to determine inorganic impurities by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Acyclovir ointment and excipients, Omeprazole tablets similar and generic samples were studied. A microwave acid digestion (MW-AD) method was optimized for a factorial design for samples of acyclovir and their effectiveness assessed by analysis of residual carbon content (RCC). In determining the method of accuracy, with the exception of Cr, the recoveries of the elements added to the samples prior to MW-AD were between 95.1 and 126%, and after the digestion step ranged from 85.6 to 132%. The limits of detection (LOD) were obtained from ng L-1 order of 0.2 to 75As+ and 91 for 58Ni+. Measurements of 75As+, 65Cu+, 52Cr+, 58Ni+, 208Pb+ and 51V+ presented a wide range varying from 2.3 ± 0.8 to 75As+ up 3446 ± 47 to 52Cr+ in g kg-1. Omeprazole samples were decomposed in two heating programs MW-AD and their efficiencies digestion measured for these matrices. Recoveries of As, Cd, Hg and Pb ranged from 75.6 to 130.0% in these samples. LD's were less than 0.07 ng L-1. Measurements of 75As+ and 208Pb+ ranged from 0.013 to 0.171 ug g-1 and 0.134 to 0.154 ug g-1, respectively; 202Hg+ and 111Cd+ are below the LD for both methods. Development of a method of ultrasound acid extraction (UAE) applied to omeprazole samples was evaluated using a factorial design and showed to be a promising alternative which employs smaller volumes of reagents, smaller extraction time, higher sample throughput being a method clean contributing to the development of green chemistry thus generating smaller volumes of chemical waste.
Brazil has a promising and growing pharmaceutical market promoting a search for high quality medicines. Agencies such as the Brazilian Health Surveillance Agency (ANVISA) in Brazil, the United States Pharmacopeia (USP) and Food and Drug Administration (FDA) and the European Medicine Agency (EMA) in the international scope describe legislation to ensure the quality of medicines in addition to control and monitoring of inorganic contaminants, especially potentially toxic inorganic elements. The main objective were the development and optimization of sample preparation methodologies applied to medicines and their manufacture products in order to determine inorganic impurities by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Acyclovir ointment and excipients, Omeprazole tablets similar and generic samples were studied. A microwave acid digestion (MW-AD) method was optimized for a factorial design for samples of acyclovir and their effectiveness assessed by analysis of residual carbon content (RCC). In determining the method of accuracy, with the exception of Cr, the recoveries of the elements added to the samples prior to MW-AD were between 95.1 and 126%, and after the digestion step ranged from 85.6 to 132%. The limits of detection (LOD) were obtained from ng L-1 order of 0.2 to 75As+ and 91 for 58Ni+. Measurements of 75As+, 65Cu+, 52Cr+, 58Ni+, 208Pb+ and 51V+ presented a wide range varying from 2.3 ± 0.8 to 75As+ up 3446 ± 47 to 52Cr+ in g kg-1. Omeprazole samples were decomposed in two heating programs MW-AD and their efficiencies digestion measured for these matrices. Recoveries of As, Cd, Hg and Pb ranged from 75.6 to 130.0% in these samples. LD's were less than 0.07 ng L-1. Measurements of 75As+ and 208Pb+ ranged from 0.013 to 0.171 ug g-1 and 0.134 to 0.154 ug g-1, respectively; 202Hg+ and 111Cd+ are below the LD for both methods. Development of a method of ultrasound acid extraction (UAE) applied to omeprazole samples was evaluated using a factorial design and showed to be a promising alternative which employs smaller volumes of reagents, smaller extraction time, higher sample throughput being a method clean contributing to the development of green chemistry thus generating smaller volumes of chemical waste.
Descrição
Palavras-chave
Preparo de amostra, Contaminantes inorgânicos, ICP-MS, Farmacopeia, Medicamentos, Sample preparation, Inorganics contaminants, Pharmacopoeia, Medicines