Análise químico-farmacêutica de cefotaxima sódica pó liofilizado para solução injetável
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Data
2016-09-30
Autores
Consortti, Lívia Paganini [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A cefotaxima sódica é um fármaco semissintético pertencente à classe das cefalosporinas de terceira geração utilizado no tratamento de meningites e outras infecções no sistema nervoso central. O fármaco é considerado seguro por interferir na síntese de uma estrutura bacteriana específica e está disponível comercialmente na forma de pó liofilizado para solução injetável. A literatura traz métodos analíticos para a determinação do teor da cefotaxima sódica com geração de resíduos tóxicos e com o emprego de reagentes que danificam os equipamentos e respectivos consumíveis. Portanto, o presente trabalho teve como objetivo o desenvolvimento de validação de métodos analíticos mais seguros aos analistas, com menor geração de resíduos e ao mesmo tempo confiáveis para assegurar as características pertinentes ao medicamento e a efetividade e segurança do tratamento. A determinação do teor de cefotaxima foi realizada pelo método por cromatografia líquida de alta eficiência e por espectroscopia no infravermelho e a potência foi determinada pelo método microbiológico turbidimétrico. O método por cromatografia líquida de alta eficiência foi desenvolvido utilizando-se fase móvel constituída por água e ácido acético na concentração de 0,1% e etanol 87:13 (V/V), o fármaco apresentou tempo de retenção de 4,4 minutos com detecção no UV em comprimento de onda de 235 nm. Na validação, a linearidade foi comprovada no intervalo de concentrações de 70 a 130 μg/mL e o método apresentou exatidão igual a 100,45% e teor de 97,87%. No método por espectroscopia no infravermelho foram confeccionadas pastilhas de brometo de potássio massa total de 200 mg e a faixa de concentração avaliada na linearidade foi de 0,4 a 0,9 mg/pastilha. A exatidão apresentou valor de 101,00% e o teor de 98,73%. O método microbiológico foi validado utilizando-se o delineamento de retas paralelas 3x3, Escherichia coli ATCC 25922, caldo BHI e água como diluente para as soluções SQR e pó liofilizado. A linearidade foi comprovada para o intervalo de concentração de 5 a 80 μg/mL, a exatidão apresentou valor de 98,98% e a potência 101,52%. Os métodos desenvolvidos apresentaram vantagens quando comparados àqueles encontrados na literatura por terem baixa geração de resíduos ao meio ambiente, uso de reagentes danosos ao equipamento e tempo de análise reduzidos. Foram validados de acordo com o preconizado pela RE n° 899, pelo guia ICH e pela FDA. Os métodos foram comparados quando à quantificação da cefotaxima sódica e não apresentaram diferença estatisticamente significativa, o que possibilita seu emprego no controle de qualidade do fármaco com segurança, confiabilidade, precisão, robustez, simplicidade e rapidez.
Sodium cefotaxime is a semisynthetic drug belonging to the class of third generation cephalosporins used in the treatment of meningitis and other infections in the central nervous system. The drug is considered safe by interfering with the synthesis of a specific bacterial structure and is commercially available as a lyophilized powder for injection. The literature provides analytical methods for the determination of cefotaxime sodium content with generation of toxic waste and using reagents that damage the equipment and relevant consumables. Therefore, this study had as aim the development and validation of safer analytical methods for analysts, with less waste and at the same time reliable to ensure the relevant characteristics to the drug and the effectiveness and safety of treatment. The determination of cefotaxime content was performed by high-performance liquid chromatography and infrared espectroscopy, and the drug activity was determined by turbidimetric microbiological method. The high-performance liquid chromatography was developed using a mobile phase consisting of water and acetic acid at a concentration of 0.1% and ethyl alcohol 87:13 (V/V) and the drug presented retention time of 4.4 minutes with UV detection at a wavelength of 235 nm. Linearity was proven in the concentrations 70 to 130 μg/mL, and the method accuracy was 100.45% and precision 97.87% for assay. The method by infrared espectroscopy was carried out with 200 mg pellets and the concentration range evaluated in linearity was 0.4 to 0.9 mg/tablet. The accuracy presented a value of 101.00% and the assay a value of 98.73%. Microbiological method was validated using the design of parallel straight 3x3, Escherichia coli ATCC 25922, BHI broth and water as a diluent for the lyophilized powder and RS solutions. The linearity was verified for the concentration range of 5 to 80 μg/mL showed the accuracy value of 98.98% and potency of 101.52%. The methods presented advantages when compared to those found in the literature because have low waste generation, use of harmful reagents to equipment and analysis time reduced, besides is according to the criteria of RE 899, ICH and FDA in the validation. Both methods were compared in quantification of cefotaxime sodium and they demonstrated no statistically significant difference, which enables the use of the same in drug quality control routine with security, reliability, accuracy, robustness, simplicity and quickness.
Sodium cefotaxime is a semisynthetic drug belonging to the class of third generation cephalosporins used in the treatment of meningitis and other infections in the central nervous system. The drug is considered safe by interfering with the synthesis of a specific bacterial structure and is commercially available as a lyophilized powder for injection. The literature provides analytical methods for the determination of cefotaxime sodium content with generation of toxic waste and using reagents that damage the equipment and relevant consumables. Therefore, this study had as aim the development and validation of safer analytical methods for analysts, with less waste and at the same time reliable to ensure the relevant characteristics to the drug and the effectiveness and safety of treatment. The determination of cefotaxime content was performed by high-performance liquid chromatography and infrared espectroscopy, and the drug activity was determined by turbidimetric microbiological method. The high-performance liquid chromatography was developed using a mobile phase consisting of water and acetic acid at a concentration of 0.1% and ethyl alcohol 87:13 (V/V) and the drug presented retention time of 4.4 minutes with UV detection at a wavelength of 235 nm. Linearity was proven in the concentrations 70 to 130 μg/mL, and the method accuracy was 100.45% and precision 97.87% for assay. The method by infrared espectroscopy was carried out with 200 mg pellets and the concentration range evaluated in linearity was 0.4 to 0.9 mg/tablet. The accuracy presented a value of 101.00% and the assay a value of 98.73%. Microbiological method was validated using the design of parallel straight 3x3, Escherichia coli ATCC 25922, BHI broth and water as a diluent for the lyophilized powder and RS solutions. The linearity was verified for the concentration range of 5 to 80 μg/mL showed the accuracy value of 98.98% and potency of 101.52%. The methods presented advantages when compared to those found in the literature because have low waste generation, use of harmful reagents to equipment and analysis time reduced, besides is according to the criteria of RE 899, ICH and FDA in the validation. Both methods were compared in quantification of cefotaxime sodium and they demonstrated no statistically significant difference, which enables the use of the same in drug quality control routine with security, reliability, accuracy, robustness, simplicity and quickness.
Descrição
Palavras-chave
Cefotaxima sódica, Controle de qualidade, Validação, Cromatografia líquida de alta eficiência, Espectroscopia no infravermelho, Método microbiológico turbidimétrico