Validation of analytical methodology for quantification of cefazolin sodium pharmaceutical dosage form by high performance liquid chromatography to be applied for quality control in pharmaceutical industry

A reversed-phase high performance liquid chromatography method was validated for the determination of cefazolin sodium in lyophilized powder for solution for injection to be applied for quality control in pharmaceutical industry. The liquid chromatography method was conducted on a Zorbax Eclipse Plus C18 column (250 x 4.6 mm, 5 μm), maintained at room temperature. The mobile phase consisted of purified water: acetonitrile (60: 40 v/v), adjusted to pH 8 with triethylamine. The flow rate was of 0.5 mL min-1 and effluents were monitored at 270 nm. The retention time for cefazolin sodium was 3.6 min. The method proved to be linear (r2=0.9999) over the concentration range of 30-80 µg mL-1. The selectivity of the method was proven through degradation studies. The method demonstrated satisfactory results for precision, accuracy, limits of detection and quantitation. The robustness of this method was evaluated using the Plackett–Burman fractional factorial experimental design with a matrix of 15 experiments and the statistical treatment proposed by Youden and Steiner. Finally, the proposed method could be also an advantageous option for the analysis of cefazolin sodium, contributing to improve the quality control and to assure the therapeutic efficacy.Um método cromatográfico em fase reversa foi validado para a determinação de cefazolina sódica em pó liofilizado, a ser aplicado no controle de qualidade em indústrias farmacêuticas. O método por cromatografia líquida foi conduzido em coluna Zorbax Eclipse Plus C18 (250 × 4,6 mm, 5 µm) mantida à temperatura ambiente. A fase móvel consistiu de água purificada: acetonitrila (60 : 40 v/v), com o pH ajustado para 8 com trietilamina. A vazão usada foi de 0,5 mL min-1 e os analitos de interesse foram monitorizados a 270 nm. O tempo de retenção da cefazolina sódica foi de 3,6 min. As áreas dos picos de cefazolina sódica foram lineares na faixa de concentração de 30-80 µg mL-1 (r2 = 0,9999). A seletividade do método foi demonstrada através de estudos de degradação. O método demonstrou resultados satisfatórios para precisão, exatidão, limites de detecção e de quantificação. A robustez do método foi avaliada utilizando o esquema fatorial de Plackett-Burman com uma matriz de 15 experimentos simultâneos, e analisados por tratamento estatístico proposto por Youden e Steiner. Finalmente, o método proposto pode ser também uma opção de êxito para a análise de cefazolina sódica, contribuindo para o controle de qualidade e para garantir a eficácia terapêutica

Análise químico-farmacêutica de cefazolina sódica em pó liofilizado para solução injetável

Os antimicrobianos têm um papel fundamental no controle de doenças infecciosas. As cefalosporinas se mantêm como uma classe de antimicrobianos que se sobressaem pela sua importância terapêutica, elevada frequência de utilização, segurança e efetividade contra um amplo espectro microbiano. A cefazolina sódica (CFZ) é um agente antimicrobiano β-lactâmico, classificada como cefalosporina de primeira geração, muito utilizado como agente terapêutico e na profilaxia perioperatória. Neste trabalho foram desenvolvidos novos métodos analíticos para análise qualitativa e para a quantificação de cefazolina sódica, visando a obtenção de métodos mais rápidos, mais seguros para os operadores, mais econômicos e de fácil execução, que são essenciais para a análise desta cefalosporina na indústria farmacêutica. Na análise qualitativa, a cefazolina foi estudada quanto a sua solubilidade, ponto de fusão, pH, espectrofotometria na região do ultravioleta (UV) e na região de infravermelho (IV), cromatografia em camada delgada e cromatografia líquida de alta eficiência (CLAE), possibilitando a identificação da amostra. Para quantificação do fármaco três métodos foram validados. O método espectrofotométrico na região do ultravioleta foi validado utilizando o comprimento de onda de 270 nm, com faixa linear de concentração de 8 a 28 μg/mL utilizando água purificada como solvente, o teor foi de 99,10% e a exatidão foi de 100,56%. Ensaio microbiológico por método turbidimétrico utilizou o micro-organismo Staphylococcus aureus ATCC 26923, com faixa linear de 6 a 11,46 μg/mL e apresentou potência de 100,07% e exatidão foi 99,92%. A validação do método por CLAE foi realizada empregando fase móvel composta por água purificada e acetonitrila (60:40 v/v), com pH 8 ajustado com trietilamina (TEA), no comprimento de onda...The antimicrobials have a crucial role in the control of infectious diseases. Cephalosporins remain one class of antimicrobials that stand out for their therapeutic importance, high frequency of use, safety and effectiveness against a broad microbial spectrum. Cefazolin sodium (CFZ) is a β-lactam antimicrobial agent, classified as first-generation cephalosporin, often used as a therapeutic agent and for perioperative prophylaxis. In this work, new analytical methods were developed for qualitative and quantitative analysis of cefazolin sodium in lyophilized powder, seeking obtain method faster, safer for operators, more economical and easiness of implementation, which are essential for the analysis of this cephalosporin in pharmaceutical industry. For qualitative analysis, several methods were performed, including analyzes of solubility, melting point and pH; ultraviolet (UV) and infrared (IR) spectrophotometry; thin layer chromatography and high performance liquid chromatography (HPLC) allowing the identification of samples. For quantification of the drug, three analytical methods were validated. The spectrophotometric method in the ultraviolet region was validated at 270 nm, with a linear range of concentration from 8 to 28 mg/mL, using purified water as solvent, the content of 99.10% accuracy of 100.56%. In the microbiological assay by turbidimetric method, Staphylococcus aureus ATCC 26923 was used as microrganism test, with linear range from 6 to 11.46 mg/mL, the method presented potency of 100.07% and accuracy of 99,92%. Validation of the HPLC method consisted of mobile phase composed of purified water and acetonitrile (60:40 v/v), adjusted to pH 8 with triethylamine (TEA), and detection wavelength of 270 nm, yielding a retention time of 3.6 minutes in the linear range evaluated from 30 to 80 μg/mL, content... (Complete abstract click electronic access below)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Methods for qualitative analysis of cefazolin sodium raw material and pharmaceutical product

In this work we studied qualitative methods for analysis and identification of cefazolin sodium, β-lactam antimicrobial for parenteral use, belonging to the group of first-generation cephalosporin, used as a therapeutic agent and for the surgical prophylaxis, in the pharmaceutical form of powder lyophilized for injectable solution. Qualitative analysis was performed by solubility, melting point, pH determination, thin layer chromatography, ultraviolet spectroscopy, infrared spectroscopy and high performance liquid chromatography, allowing the identification of sample. These methods were reproducible and quick to identify cefazolin sodium, which can be used routinely in analysis of quality control in pharmaceutical laboratories.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

A critical review of analytical methods for determination of ertapenem sodium

Antimicrobials have unquestionable importance in the control of many diseases; however the constant concern with evolution of resistant microorganisms is increasing. The ertapenem sodium is a β-lactam antibiotic of the carbapenem class, which it has a broader activity spectrum than most other β-lactam antimicrobials, and is more resistant to the enzyme β-lactamase, which is the main mechanism of resistance of many bacteria. The progress of microbial resistance to existing antibiotics is alarming. Thus we need to preserve antimicrobials that still have activity against these pathogens. In this context, the quality control has a key role to ensure the correct dosage, by contributing preventively to minimize the development of resistant microorganisms. Study of the physicochemical characteristics of the drug and the quantification of the content of active substance are of fundamental importance for the pharmaceutical industry to ensure the quality of the product sold. This work presents a literature survey of existing methods for ertapenem sodium quantification which was performed. Ertapenem sodium can be analyzed by many types of assays; however the HPLC is the most used method. This review will examine the published analytical methods reported for determination of ertapenem sodium, in biological fluids and formulations

Development and validation of a microbiological assay by turbidimetry to determine the potency of cefazolin sodium in the lyophilized powder form

In many countries, high rates of mortality and morbidity from infectious diseases represent high social and economic costs. Cefazolin sodium is a semi-synthetic beta-lactam antimicrobial for parenteral use, belonging to the first-generation cephalosporin's group. Its use in clinical practice stands out for its effectiveness as a therapeutic agent and in surgical prophylaxis, having great importance in the fight against many diseases. This paper reports the development and validation of an efficient, accurate, reproducible, and low cost microbiological assay by a turbidimetric method to quantify cefazolin in the lyophilized powder form. These requirements are essential for the analysis of this cephalosporin in the pharmaceutical industry. The assay is based on the inhibitory effect of cefazolin sodium upon the strain of Staphylococcus aureus ATCC 26923 used as the test microorganism. The method was validated according to the ICH guidelines and the results were treated by analysis of variance (ANOVA), proving to be linear (r(2) = 0.9999 for the reference substance and r(2) = 0.9995 for the sample), in the selected range from 6 to 11.76 mu g mL(-1), precise (RSD values < 2.0%), robust and accurate (99.92%). The developed method showed excellent validation results, and the statistical analysis corroborated with its assessment. Furthermore, Student's t-test showed no statistically significant difference between the proposed turbidimetric method and an UV spectrophotometry method previously validated. Thus, the validated method is able to quantify cefazolin sodium in the powder form for injectable solution, while being an economical and rapid alternative for its routine analysis in quality control.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Application of the Principles of Green Chemistry for the Development of a New and Sensitive Method for Analysis of Ertapenem Sodium by Capillary Electrophoresis

An innovative method is validated for the analysis of ertapenem sodium by capillary electrophoresis using potassium phosphate buffer 10 mM pH 7 and 15 kV voltage, in the concentration range of 70 to 120 μg mL−1. Ertapenem had a migration time of 3.15 minutes and the linearity curve was y = 2281.7 x - 24495 with a R2 = 0.9994. Thus, we propose a routine analysis method that meets the principles of green analytical chemistry for the routine analysis of ertapenem sodium by capillary electrophoresis

Application of the Principles of Green Chemistry for the Development of a New and Sensitive Method for Analysis of Ertapenem Sodium by Capillary Electrophoresis

An innovative method is validated for the analysis of ertapenem sodium by capillary electrophoresis using potassium phosphate buffer 10 mM pH 7 and 15 kV voltage, in the concentration range of 70 to 120 μg mL-1. Ertapenem had a migration time of 3.15 minutes and the linearity curve was y = 2281.7 x - 24495 with a R2 = 0.9994. Thus, we propose a routine analysis method that meets the principles of green analytical chemistry for the routine analysis of ertapenem sodium by capillary electrophoresis.status: publishe

Semiologia farmacêutica e os desafios para sua consolidação

Pharmaceutical semiology can be comprehended as the identification of signs and symptoms, especially those related to minor disturbances/disorders reported by the patients. This practice should not be confused with diagnosis, which is an activity performed by the doctor, but as a new tool in the active dispensing of prescription drugs. This study aims to identify the development of this practice and discuss the challenges required for its implementation.La semiología farmacéutica puede ser entendida como la identificación de los signos y síntomas, en especial los relacionados con los trastornos / alteraciones menores reportados por el paciente. Esta práctica profesional no debe ser confundido con el diagnóstico, que es una actividad realizada por el médico, sino como una nueva herramienta de dispensación en los medicamentos de venta libre. Este estudio tiene como objetivo identificar el desarrollo de esta práctica profesional y discutir los retos necesarios para su aplicación.A semiologia farmacêutica pode ser entendida como a identificação de sinais e sintomas, principalmente aqueles relacionados aos transtornos/distúrbios menores relatados pelo paciente. Essa prática profissional não deve ser confundida com diagnóstico, que é uma atividade realizada pelo médico, mas como uma nova ferramenta na dispensação ativa de medicamentos de venda livre. Este estudo visa identificar o desenvolvimento dessa prática profissional e discutir os desafios necessários à sua implementação.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP