DETERMINATION OF PINAVERIUM BROMIDE IN PHARMACEUTICAL DOSAGE FORMS BY A VALIDATED STABILITY-INDICATING LC METHOD

A reversed-phase liquid chromatography (LC) method is validated for the determination of pinaverium bromide (PB) in pharmaceutical dosage forms. The LC method is carried out on a reversed-phase monolithic C18 column (100 x 4.6 mm i.d.), maintained at 45 ºC. The mobile phase consisted of acetonitrile and a solution of triethylamine 0.3% pH 5.0 (50:50; v/v), run at a flow rate of 2.0 mL/min, with photodiode array detector set at 213 nm. The chromatographic separation is obtained with PB retention time of 3.4 min, and it is linear in the range of 5-100 μg/mL (r2 = 0.9991). The limits of detection and quantitation are 1.41 and 4.70 μg/mL, respectively. The specificity and stability-indicating capability of the method are proven through degradation studies, which also showed that there is no interference of the formulation excipients, showing that peak is free from any coeluting peak. The method showed adequate precision, with a relative standard deviation values lower than 1.38%. Excellent values of accuracy were also obtained, with a mean value of 100.68%. Experimental design is used during validation to calculate and prove method robustness. The proposed LC method is applied for the analysis of the PB pharmaceutical dosage forms, contributing to improve the quality control and to assure the therapeutic efficacy

Validation of a green spectrophotometric method for the determination of dropropizine in commercial oral solutions

The present work describes a first-order derivative spectrophotometric (1D-UV) method for determination of dropropizine in commercial oral solutions. The method was developed using ecologically correct solvents and validated according to International Conference on Harmonization (ICH) recommendations. The response was linear in the concentration range of 6–24 μg/mL (r = 0.9997, n = 7) at wavelength 249 nm, which was the zero crossing point of excipient solutions. The detection and quantitation limits were 0.36 and 1.18 μg/mL, respectively. The method showed adequate precision, with a relative standard deviation values lower than 1.41%. Excellent values of accuracy were obtained, with a mean value of 99.44%. The method proved to be robust by a full factorial design evaluation. It is simple, it has low cost, and it has low use of polluting reagents. Minimum environmental hazards observed and the results obtained attest to the reliability of the proposed green method, showing to be specific, linear, precise, accurate and robust. Thus, the validated 1D-UV spectrophotometric method was successfully applied to the quantitative analysis of dropropizine in oral solutions dosage forms, helping to improve quality control and to assure therapeutic efficacy

Determination of phenobarbital in human plasma by a specific liquid chromatography method: application to a bioequivalence study

A liquid chromatography method was developed and validated for the determination of phenobarbital in human plasma using phenytoin as internal standard. The drugs were extracted from plasma by liquid-liquid extraction and separated isocratically on a C12 analytical column, maintained at 35 ºC, with water:acetonitrile:methanol (58.8:15.2:26, v/v/v) as mobile phase, run at a flow rate of 1.2 mL/min with detection at 205 nm. The method was linear in the range of 0.1-4 μg/mL (r²=0.9999) and demonstrated acceptable results for the precision, accuracy and stability studies. The method was successfully applied for the bioequivalence study of two tablet formulations (test and reference) of phenobarbital 100 mg after single oral dose administration to healthy human volunteers

Fesoterodina : desenvolvimento de metodologia analítica, ensaio de dissolução e estudo da estabilidade

O fumarato de fesoterodina (FESO) é um potente fármaco antimuscarínico recentemente desenvolvido para o tratamento da síndrome da bexiga hiperativa, também conhecida como incontinência urinária. A análise de fármacos é necessária em todas as fases do desenvolvimento farmacêutico, como estabilidade e controle de qualidade dos produtos comercializados. Nenhum relato de determinação quantitativa e de estudos de estabilidade do fármaco em comprimidos foi encontrado na literatura. No presente trabalho, a caracterização da substância química de referência de FESO foi realizada por espectrometria de massas e ressonância magnética nuclear de hidrogênio. Métodos analíticos por espectrofotometria derivada, cromatografia líquida de alta eficiência (CLAE), eletroforese capilar e cromatografia líquida acoplada à espectrometria de massas sequencial foram desenvolvidos para determinação qualitativa e quantitativa de FESO em comprimidos de liberação prolongada. Os procedimentos foram validados, avaliando-se os parâmetros de especificidade, linearidade, precisão, exatidão, robustez e limite de detecção e quantificação, cujos resultados cumpriram os requisitos preconizados. Os resultados obtidos através destes métodos foram comparados estatisticamente por ANOVA, que indicou não haver diferenças estatisticamente significativas entre os mesmos. A cinética de fotodegradação da FESO também foi avaliada utilizando o método por CLAE, na qual foi obtido um modelo de ordem zero. Um método por cromatografia líquida acoplada à espectrometria de massas foi aplicado para análise de FESO e de seus produtos de degradação, possibilitando identificar os íons moleculares destes e propor a rota de fragmentação do fármaco. Além disso, desenvolveu-se e validou-se um método de dissolução de FESO em comprimidos. Através deste método, foi observado que a formulação possui uma cinética de dissolução de acordo com o modelo de Higuchi. Desse modo, estabeleceram-se procedimentos que podem ser aplicados para aprimorar o controle da qualidade dos medicamentos comercializados, bem como contribuir para garantir a segurança e eficácia no uso terapêutico.Fesoterodine fumarate (FESO) is a potent antimuscarinic drug recently developed for the treatment of overactive bladder, a lower urinary tract disorder characterized by urinary urgency. The drug analysis is necessary in all steps of the pharmaceutical development, as stability and quality control tests of marketed products. The absence of the reports in the literature of quantitative determination and stability studies of the drug in pharmaceutical formulation were observed. In the present study, the characterization of the FESO reference substance was performed by mass spectrometry and proton nuclear magnetic resonance techniques. Analytical methods by derivative spectrophotometry, liquid chromatography (LC), capillary electrophoresis and liquid chromatography coupled to tandem mass spectrometry were developed for qualitative and quantitative determination of FESO in extended-release tablets. The procedures were validated, evaluating the parameters of specificity, linearity, precision, accuracy, robustness, and limit of detection and quantitation, whose results have met the requirements recommended. The results obtained through these analytical methods were compared by ANOVA, which showed no significant statistically difference between them. The photodegradation kinetic of FESO was also evaluated using the validated LC method, following the zero-order kinetics. A liquid chromatography coupled to mass spectrometry method was applied for analysis of FESO and its degradation products, enabling to identify the respective molecular ions and propose the drug photodegradation pathway. Besides, a dissolution method for FESO extended-release tablets was developed and validated. It method allowed to observe that the kinetics of drug release of the presented pharmaceutical formulation was better described by the Higuchi model. Then, the established procedures can be applied to improve the quality control of the commercialized pharmaceutical formulations, as well as to contribute for assure the safety and therapeutic efficacy of the drug

Development and validation of an UV spectrophotometric method for the determination of aliskiren in tablets

For determination of aliskiren in commercial samples, an analytical UV spectrophotometric method was developed and validate according to ICH guideline. The method was linear in the range between 40 and 100 μg mL-1 (r² = 0.9997, n = 7) and exhibited suitable specificity, accuracy, precision, and robustness. It is simple, it has low cost, and it has low use polluting reagents. Therefore, the proposed method was successfully applied for the assay and dissolution studies of aliskiren in tablet dosage forms, and the results were compared to a validated RP-LC method, showing non-significant difference (P > 0.05)

DETERMINATION OF PINAVERIUM BROMIDE IN PHARMACEUTICAL DOSAGE FORMS BY A VALIDATED STABILITY-INDICATING LC METHOD

A reversed-phase liquid chromatography (LC) method is validated for the determination of pinaverium bromide (PB) in pharmaceutical dosage forms. The LC method is carried out on a reversed-phase monolithic C18 column (100 x 4.6 mm i.d.), maintained at 45 ºC. The mobile phase consisted of acetonitrile and a solution of triethylamine 0.3% pH 5.0 (50:50; v/v), run at a flow rate of 2.0 mL/min, with photodiode array detector set at 213 nm. The chromatographic separation is obtained with PB retention time of 3.4 min, and it is linear in the range of 5-100 μg/mL (r2 = 0.9991). The limits of detection and quantitation are 1.41 and 4.70 μg/mL, respectively. The specificity and stability-indicating capability of the method are proven through degradation studies, which also showed that there is no interference of the formulation excipients, showing that peak is free from any coeluting peak. The method showed adequate precision, with a relative standard deviation values lower than 1.38%. Excellent values of accuracy were also obtained, with a mean value of 100.68%. Experimental design is used during validation to calculate and prove method robustness. The proposed LC method is applied for the analysis of the PB pharmaceutical dosage forms, contributing to improve the quality control and to assure the therapeutic efficacy

Development and Validation of A Stability-Indicating Mekc Method for Determination of Flucloxacillin Sodium in Capsules

Flucloxacillin (FLU) is a semi-synthetic penicillin active against Gram-positive bacteria such as streptococci and penicilinase-producing staphylococci, including methicillin-susceptible S. aureus. A simple, rapid and reproducible stability-indicating micellar electrokinetic chromatography (MEKC) method was developed and validated for analysis of flucloxacillin sodium in capsules, using nimesulide as internal standard. The MEKC method was performed on a fused-silica capillary (50 mu m id; effective length of 40 cm). The background electrolyte consists of 50 mM borate and 80 mM anionic surfactant SDS quantities at pH 8.5. The separation was achieved at 20 kV applied voltage and 27.5 degrees C. The injection was performed using the hydrodinamic mode at 50 mbar for 4s, with detection at 210 nm. The method was linear in the range of 20-100 mu g mL(-1) (r = 0.9996) with adequate results for the precision ( 0.005). The proposed method might be applied in routine quality control in the pharmaceutical industries.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES