A green approach for the quantification of daptomycin in pharmaceutical formulation by UV spectrophotometry

Daptomycin is the first approved drug from a new class of antimicrobials, the cyclic lipopeptides, and is a very important antimicrobial agent in current clinical practice. Currently, there are no "green" analytical methods described in the literature to analyze the typical pharmaceutical dosage form of daptomycin. Thus, the aim of this work was to validate an environment-friendly spectrophotometric method in the UV region, for the analysis of daptomycin as a lyophilized powder. Water was used as diluent and the analyses were carried out on a spectrophotometer at 221 nm. The method met all validation requirements of the ICH guidelines, over a concentration range of 6-21 µg mL-1. A Student's t-test demonstrated that the proposed method was comparable to an HPLC method previously validated. Thus, the validated spectrophotometric method could quantify daptomycin in a powder form for injectable solutions, while being an economical, rapid, and "green" alternative for routine analysis in quality control.A daptomicina é o primeiro membro aprovado de uma nova classe de antimicrobianos, os lipopeptídeos cíclicos, e é muito importante para a prática clínica atualmente. Não existem métodos analíticos "verdes" descritos na literatura para a análise da daptomicina na forma farmacêutica. Desta forma, o objetivo deste trabalho foi a validação de método espectrofotométrico na região do UV ambientalmente favorável para análise da daptomicina em pó liofilizado. A água foi escolhida como diluente e as análises foram realizadas em 221 nm. O método atendeu a todas as exigências de validação dos guias do ICH, na faixa de 6-21 µg mL-1. Teste t de Student mostrou que o método proposto é intercambiável com método de HPLC previamente validado. Assim, o método espectrofotométrico validado é capaz de quantificar a daptomicina em pó para solução injetável e é uma opção econômica, rápida e "verde" para análises de rotina do controle de qualidade deste fármaco

Verificação da Qualidade Microbiológica de Medicamentos Contendo Paracetamol Encontrados em Algumas Residências de Américo Brasiliense/Sp

It is known that a high microbial count can compromise the stability of medicines, thus reducing their therapeutic efficacy. This work tried to demonstrate that the microbial contamination can be directly related to the inadequate handling of the medicines stored in homes, making it possible to draw strategies to reduce the possible risks of medical therapy offering correct information and advising. The objective of this work was to evaluate the quality of the medicines containing paracetamol found in the residences of Américo Brasiliense-SP, using the microbial analysis of non-sterile method described in the Brazilian Pharmacopoeia (1988). The medicine samples (30 samples) were obtained directly from the interviewed local residents, who had received new medicine bottles of the same product. An analysis of viable microorganisms (bacteria and fungus) was carried out to identify pathogens found in the collected samples. Although 90% of the analyzed samples have shown some microbial contamination, the results indicated the absence of pathogenic microorganisms, and the total count of viable microorganisms was below the maximum value for non-sterile (104 UFC/g or mL). It was also verified that the local residents stored the medicines in appropriate places, according to the orientations received when they bought the medicines in pharmacies and drugstores, showing the importance of information for the correct use and conservation of pharmaceuticals.Sabe-se que elevadas cargas microbianas podem comprometer a estabilidade de medicamentos, prejudicando sua eficácia terapêutica. O presente trabalho buscou demonstrar que a contaminação microbiana pode estar diretamente envolvida com a manipulação inadequada dos medicamentos mantidos nas residências, tornando possível traçar estratégias para reduzir possíveis riscos à terapia medicamentosa, por meio de orientação e informação adequadas. O objetivo deste trabalho foi avaliar a qualidade microbiológica de medicamentos em gotas contendo paracetamol encontrados em residências de Américo Brasiliense/SP, através do método de análise para produtos não-estéreis descrito na Farmacopeia Brasileira (1988). As amostras de medicamento em uso (30 amostras) foram obtidas diretamente dos moradores entrevistados, que receberam frascos novos do mesmo produto. Foram realizadas a contagem de micro-organismos viáveis (bactérias e fungos) e a pesquisa e identificação de patógenos nas amostras coletadas. Apesar de 90% das amostras apresentarem contaminação, os resultados indicaram ausência de micro-organismos patogênicos, bem como contagem total de microorganismos viáveis abaixo do valor máximo permitido para produtos não-estéreis (104 UFC/g ou mL) nas amostras analisadas. Também foi verificado que os moradores entrevistados armazenavam os medicamentos em locais apropriados, de acordo com as orientações recebidas no momento da aquisição dos mesmos nas farmácias e drogarias, ressaltando a importância da informação para o correto uso e conservação de medicamentos

A green approach for the quantification of daptomycin in pharmaceutical formulation by UV spectrophotometry

abstract Daptomycin is the first approved drug from a new class of antimicrobials, the cyclic lipopeptides, and is a very important antimicrobial agent in current clinical practice. Currently, there are no "green" analytical methods described in the literature to analyze the typical pharmaceutical dosage form of daptomycin. Thus, the aim of this work was to validate an environment-friendly spectrophotometric method in the UV region, for the analysis of daptomycin as a lyophilized powder. Water was used as diluent and the analyses were carried out on a spectrophotometer at 221 nm. The method met all validation requirements of the ICH guidelines, over a concentration range of 6-21 µg mL-1. A Student's t-test demonstrated that the proposed method was comparable to an HPLC method previously validated. Thus, the validated spectrophotometric method could quantify daptomycin in a powder form for injectable solutions, while being an economical, rapid, and "green" alternative for routine analysis in quality control

Análise químico-farmacêutica de preparações injetáveis de ampicilina sódica

A ampicilina sódica é um antimicrobiano β-lactâmico, semi-sintético, de uso parenteral, pertencente ao grupo das penicilinas. Trata-se da primeira penicilina semi-sintética a apresentar atividade contra bacilos Gram-negativos, abrindo o campo de penicilinas de amplo espectro. Existem vários trabalhos na literatura que descrevem métodos analíticos para análise da ampicilina em formas farmacêuticas. A maior parte deles envolve a cromatografia líquida de alta eficiência (CLAE) com fases móveis constituídas por soluções-tampão, as quais podem danificar as colunas cromatográficas, ou métodos que envolvem o gasto de grandes quantidades de solventes orgânicos. No entanto, a tendência é que as indústrias busquem minimizar e/ou eliminar o uso de solventes orgânicos de seus processos com o objetivo de reduzir os impactos de suas atividades sobre o meio ambiente. Desta forma, este trabalho teve como objetivo principal o desenvolvimento de novos métodos analíticos para análise de ampicilina sódica na forma farmacêutica de pó liofilizado para solução injetável, que apresentem menor impacto sobre o meio ambiente e que sejam mais práticos, mais seguros para os operadores e mais econômicos que as metodologias analíticas já descritas para a ampicilina. A ampicilina sódica foi analisada qualitativamente quanto à umidade e solubilidade. Também foi realizada análise por espectrofotometria no infravermelho e desenvolvido método por cromatografia em camada delgada (CCD) indicativo de estabilidade. Quanto à análise quantitativa, foi validado método por CLAE com detecção ultravioleta (UV) a 210 nm, fase móvel composta por etanol e água (40:60, v/v) e faixa de concentração de 70,0 a 120,0 μg/mL, exatidão de 99,54%, teor de 96,83% e tempo de retenção médio de 3,1 minutos; ensaio microbiológico pelo método...Ampicillin sodium is a semi-synthetic β-lactam antibiotic for parenteral use, belonging to the penicillin group. It was the first semi-synthetic penicillin to show any action against Gram-negative bacilli, opening a field of broad spectrum penicillins. There are several published studies in literature that describe analytical methods for ampicillin in pharmaceutical dosage forms. Most of them are related to high performance liquid chromatography (HPLC) using mobile phases constituted by buffer solutions, which may damage the chromatographic columns over time, or methods that involve, mostly, the use of large amounts of organic solvents. However, the tendency is that industries seek to minimize or eliminate the use of organic solvents in their processes in order to reduce the impacts of their activities on the environment. In this way, this study aimed to develop new analytical methods for the analysis of ampicillin sodium in lyophilized powder for injectable solution, which have the lowest impact on the environment as possible and that be more convenient, safer for operators and more economical than the analytical methodologies already described for ampicillin. Ampicillin sodium was analyzed qualitatively as the moisture content and solubility characteristics. Furthermore, it was performed an analysis by infrared spectroscopy and was developed a stability indicative method by thin layer chromatography (TLC). Regarding the quantitative analysis, it was validated HPLC methodology with UV detection at 210 nm, mobile phase composed by ethanol and water (40:60 v /v), the concentration range from 70.0 to 120.0 μg/mL, accuracy of 99.54%, content of 96.83% and average retention time of 3.1 minutes; microbiological assay by turbidimetric method, in the concentration range from 2.0 to 8.0 μg/mL, using Staphylococcus aureus ATCC 26923, with accuracy... (Complete abstract click electronic access below)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Rapid turbidimetric assay to determine the potency of daptomycin in lyophilized powder

Daptomycin is an important antimicrobial for clinical practice, mainly because it remains very active against Gram-positive resistant strains, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Development of microbiological methods for the analysis of antimicrobials is highly recommended, since they can provide important information about their biological activities, which physicochemical methods are not able to provide. Considering that there are no studies in the literature describing microbiological methods for the analysis of daptomycin, the aim of this work was to validate a microbiological method for the quantitation of daptomycin by the turbidimetric assay. Staphylococcus aureus was used as the test microorganism, and the brain heart infusion broth was used as the culture medium. The validation of the method was performed according to the ICH guidelines, and it was shown to be linear, precise, robust, accurate and selective, over a concentration range of 8.0 to 18.0 µg mL-1. Student's t-test showed the interchangeability of the proposed method with a previously-validated HPLC method. The developed turbidimetric method described in this paper is a convenient alternative for the routine quality control of daptomycin in its pharmaceutical dosage form.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Development of an innovative, ecological and stability-indicating analytical method for semiquantitative analysis of ampicillin sodium for injection by thin layer chromatography (TLC)

Ampicillin sodium is a β-lactam antimicrobial agent for parenteral use, widely used in many parts of the world and recommended by the World Health Organization. There are some methods described in the literature to identify ampicillin sodium employing Thin-Layer Chromatography (TLC). However, these methods are complex and require the use of solvents potentially toxic to the operators and environment. This paper describes the validation of an innovative semiquantitative method for the analysis of ampicillin sodium in powder for injectable solution, using TLC. This technique does not use toxic or expensive solvents, which is one great advantage over the described TLC analytical methods. This fact contributes to minimize the generation of toxic organic solvent waste by the industry and thereby reduces the impact of its activities on the environment. The method involved the use of a mobile phase comprised by a mixture of ethanol and water (90:10, v/v) and the stationary phase was silica gel impregnated in aluminum. Stress degradation studies of the pharmaceutical product were conducted under conditions of hydrolysis (acid, basic, and aqueous), oxidation and photolysis. The spots were detected by exposing the dry plate to UV chamber (254 nm) and/or iodine vapor and analyzed semiquantitatively by HPLC-UV. The method was successfully validated according to the ICH guidelines and Brazilian legislation, showing to be able to semiquantify ampicillin sodium in powder for injection preparation and it can be used as an environmentally friendly alternative for the routine analysis in quality control.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Development and validation of the quantitative analysis of ampicillin sodium in powder for injection by Fourier-transform infrared spectroscopy (FT-IR)

This paper describes the validation of an innovative analytical method for ampicillin sodium in powder for injection quantification, using Fourier-transform infrared (FT-IR) transmission spectroscopy. This technique does not use organic solvents, which is one great advantage over the most common analytical methods. This fact contributes to minimize the generation of organic solvent waste by the industry and thereby reduces the impact of its activities on the environment. The method involved absorbance measurements of the band corresponding to one of the carbonyl groups in the molecule, centered in the region between 1800 and 1700 cm-1 . The method was validated according to ICH guidelines, showing to be linear (r = 0.9993), precise, accurate and robust, over a concentration range from 1.0 to 3.0 mg. The validated method is able to quantify ampicillin sodium in powder for injection preparation and can be used as an environmentally friendly alternative for the routine analysis in quality control.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

A importância da atenção farmacêutica após a verificação da qualidade microbiológica de medicamentos contendo paracetamol encontrados em algumas residências de Américo Brasiliense - SP

It is known that a high microbial count can compromise the stability of medicines, thus reducing their therapeutic efficacy. This work tried to demonstrate that the microbial contamination can be directly related to the inadequate handling of the medicines stored in homes, making it possible to draw strategies to reduce the possible risks of medical therapy offering correct information and advising. The objective of this work was to evaluate the quality of the medicines containing paracetamol found in the residences of Américo Brasiliense-SP, using the microbial analysis of non-sterile method described in the Brazilian Pharmacopoeia (1988). The medicine samples (30 samples) were obtained directly from the interviewed local residents, who had received new medicine bottles of the same product. An analysis of viable microorganisms (bacteria and fungus) was carried out to identify pathogens found in the collected samples. Although 90% of the analyzed samples have shown some microbial contamination, the results indicated the absence of pathogenic microorganisms, and the total count of viable microorganisms was below the maximum value for non-sterile (104 UFC/g or mL). It was also verified that the local residents stored the medicines in appropriate places, according to the orientations received when they bought the medicines in pharmacies and drugstores, showing the importance of information for the correct use and conservation of pharmaceuticals.Sabe-se que elevadas cargas microbianas podem comprometer a estabilidade de medicamentos, prejudicando sua eficácia terapêutica. O presente trabalho buscou demonstrar que a contaminação microbiana pode estar diretamente envolvida com a manipulação inadequada dos medicamentos mantidos nas residências, tornando possível traçar estratégias para reduzir possíveis riscos à terapia medicamentosa, por meio de orientação e informação adequadas. O objetivo deste trabalho foi avaliar a qualidade microbiológica de medicamentos em gotas contendo paracetamol encontrados em residências de Américo Brasiliense/SP, através do método de análise para produtos não-estéreis descrito na Farmacopeia Brasileira (1988). As amostras de medicamento em uso (30 amostras) foram obtidas diretamente dos moradores entrevistados, que receberam frascos novos do mesmo produto. Foram realizadas a contagem de micro-organismos viáveis (bactérias e fungos) e a pesquisa e identificação de patógenos nas amostras coletadas. Apesar de 90% das amostras apresentarem contaminação, os resultados indicaram ausência de micro-organismos patogênicos, bem como contagem total de microorganismos viáveis abaixo do valor máximo permitido para produtos não-estéreis (104 UFC/g ou mL) nas amostras analisadas. Também foi verificado que os moradores entrevistados armazenavam os medicamentos em locais apropriados, de acordo com as orientações recebidas no momento da aquisição dos mesmos nas farmácias e drogarias, ressaltando a importância da informação para o correto uso e conservação de medicamentos