Liquid chromatography-mass spectrometry for simultaneous determination of spironolactone and canrenone in plasma samples

In our study, we aimed to validate a method based on liquid chromatography-mass spectrometry (LC-MS) to quantify spironolactone (SPI) and its active metabolite canrenone (CAN) simultaneously in plasma samples to support in vivo experiments. Compounds were separated by using a C18 column with the isocratic elution of a mobile phase composed of 0.1% (v/v) formic acid in methanol-water (60:40 v/v) at a flow rate of 0.4 mL min−1. SPI and CAN were detected in na electrospray interface operating in a positive ionization mode and quantified using the selective ion mode monitoring of mass-charge ratios (m/z) of 439.0 for SPI and 363.1 for CAN. After calculating the matrix effect using theoretical equations, we observed the strong interference of plasma in the equipment-generated signal, which required creating analytical curves using the matrix as a solvent. The method was nevertheless linear (r 2 > 0.999) in a concentration range of 0.4-5.0 μg mL−1, as well as precise, with a coefficient of variation less than 5%. SPI’s and CAN’s recovery rates from the plasma ranged from 87.4% to 112.1%, while their limits of detection (i.e., 0.07 μg mL−1 and 0.03 μg mL−1, respectively) and quantification (i.e., 0.20 μg mL−1 and 0.08 μg mL−1, respectively) in the presence of plasma contaminants were low. Therefore, the bioanalytical method seems to be feasible for quantifying SPI and CAN in plasma

As boas práticas de fabricação de medicamentos e suas determinantes

Good Manufacturing Practices (GMP) ensure that drugs are consistently produced and controlled according to previously established quality standards. They are designed to manage and minimize the inherent risks involved in the manufacture of drugs in order to ensure the quality, efficacy and safety of the finished product. Since their inception as we know them today, several versions have taken place in Brazil and worldwide. This work proposes to analyze GMP, through the analysis of the content of Brazilian regulatory frameworks, identifying the determinants that can explain their evolution over the last decades. GMP were broken down into topics and subtopics and their versions present in the five regulatory frameworks studied were evaluated. It was possible to verify, in the evolution of drug manufacturing requirements, the interference of technological innovation and the influence of new practices related to quality, identifying the GMP transformation dynamics.As Boas Práticas de Fabricação (BPF) garantem que os medicamentos sejam consistentemente produzidos e controlados de acordo com padrões de qualidade previamente estabelecidos. Têm por objetivo gerenciar e minimizar os riscos inerentes à fabricação de medicamentos com vista a garantir a qualidade, eficácia e segurança do produto acabado. Desde o seu surgimento da forma como conhecemos hoje, várias versões se sucederam no Brasil e no mundo. Esse trabalho se propõe a analisar as BPF, por meio da análise de conteúdo dos marcos regulatórios brasileiros, identificando as determinantes que podem explicar a sua evolução através das últimas décadas. As BPF foram decompostas em temas e subtemas e suas versões, presentes nos cinco marcos regulatórios estudados, foram avaliadas. Foi possível comprovar, na evolução dos requisitos de fabricação de medicamentos, a interferência da inovação tecnológica e a influência de novas práticas relacionadas à qualidade, identificando, dessa forma, a dinâmica de transformação das BPF

Recent advances in the treatment of Chagas disease

Descoberta há cem anos, a doença de Chagas afeta a mais de quinze milhões de pessoas em toda a América Latina e, ainda hoje, não há tratamentoeficaz. O fármaco benznidazol, utilizado como única opção de tratamento no Brasil, é ineficaz na fase crônica da doença. Problemas relacionados à biodisponibilidade do medicamento comercial limitam sua eficácia, principalmente na fase crônica, quando os parasitos estão confinados em tecidos profundos e em lenta replicação. Nesse contexto, pesquisas lideradas por grupos brasileiros e argentinos vêm sendo conduzidas com o objetivo de desenvolver formulações de benznidazol mais eficientes. Diversas formas farmacêuticas sólidas e líquidas foram propostas nos últimos anos com resultados pré-clínicos promissores, sendo descritas melhorias acentuadas nas características farmacocinéticas desse fármaco. Espera-se que as formas inovadoras apresentadas possam ser avaliadas em ensaios clínicos e incorporadas à produção industrial em breve.Discovered about a hundred years ago, Chagas disease currently affects more than fifteen million people in Latin America, and it still remains without any effective treatment. Although benznidazole has been used as the only pharmacotherapeutic option to treat Chagas disease in Brazil, it is ineffective in the chronic phase of the disease, when the parasites are confined to deep tissue layers and slowly replicate. This happens mainly due to problems related to the bioavailability of the drug, which is currently in the market. In this context, Brazilian and Argentinean research groups have conducted studies to develop more efficient benznidazole formulations. Several solid and liquid formulations have been proposed over the last few years with promising preclinical results. Improvements in the pharmacokinetic properties of this drug have been described. Therefore, it is expected, that such innovative drugs and formulations be assessed in clinical trials and soon incorporated to industrial production.Fil: da Cunha Filho, Marcílio Sérgio Soares . Universidade Do Brasilia; BrasilFil: de Sá-Barreto, Lívia Cristina lira . Universidade Do Brasilia; BrasilFil: Leonardi, Darío. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Lamas, Maria Celina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Salomon, Claudio Javier. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentin

Caracterização físico-química do fármaco antichagásico benznidazol

Currently, benznidazole (BNZ) is a unique therapeutic alternative available in Brazil to treat Chagas disease. Despite its traditional medical use, little is known about the chemical nature of this drug. A detailed study of the physicochemical properties of BNZ was performed using multiple assays. Thermal, diffractometric, morphological and reological drug profiles were obtained. The partition coefficient and solubility results allowed this drug to be classified as a class IV drug according to the biopharmaceutical classification system. This information will be useful for the development of more effective BNZ formulations and for establishing the quality profile of BNZ

Benznidazole

The conformation of the title compound [systematic name: N-benzyl-2-(2-nitro­imidazol-1-yl)acetamide], C12H12N4O3, can be described in terms of the relative orientation of three planar fragments, the imidazol group (A), benzyl group (B), and the acetamide fragment (C), with corresponding dihedral angles: A/C = 88.17 (4), B/C = 67.12 (5) and A/B = 21.11 (4)°. The crystal packing is enhanced by a network of strong inter­molecular N—H⋯O hydrogen bonds

Cortes comerciales y característica de la canal de borregos y cabritos suplementados con bloques multinutricionales

 Objective. Aimed to identify the weight and yield of the commercial cuts, muscularity, and adiposity in the carcasses of sheep and goats grazing in the Caatinga supplemented with different sources of supplementations; these include feed-blocks. Material and methods. Sixty non-castrated males an initial average body weight of 18.63 ± 1.93 kg were used: 30 goats and 30 sheep all animals did not have a defined breed standard (WDBS). The experimental design used was entirely randomized (DIC), in factorial scheme 3x2 (three types of supplementation: mineral salt, MBs and MBs + buffel hay, and two species: sheep and goats) and 10 replications. Animals were raised in a rangeland grazing system in an area with vegetation characteristic of Caatinga ecosystem under three types of supplementation: 1: only mineral salt; 2: Feed blocks (MBs); and 3: MBs + buffel hay There were measured the weight, yield and the components of left half-part of carcass of lambs and kids. Results. The sheep were superior to goats in carcass conformation, loin-eye area, index of muscularity of the leg and compactness index of the leg while the goats were superior to sheep in leg muscles weight. Conclusions. Sheep and Goats, when fed with supplementation of pasture feeding blocks in the Caatinga ecosystem; Supplementation with mineral salt and Multinutritional Blocks with and without Buffel can be used to improve herds in the caatinga, with similar results among the three. Sheep show more adiposity of meat than goats, in contrast, goats have higher musculature than sheep when fed with feed blocks.Objetivo. Con el objetivo de identificar el peso y rendimiento de los cortes comerciales, musculatura y adiposidad en las canales de borregos y cabritos pastando en la Caatinga suplementado con diferentes fuentes de suplementos; Estos incluyen bloques de alimentación. Material y métodos. Se utilizaron 60 machos no castrados con un peso corporal medio inicial de 18,63 ± 1,93 kg: 30 borregos y 30 cabritos, todos los animales no tenían un estándar de raza definido (WDBS). El diseño experimental utilizado fue totalmente al azar (DIC), en esquema factorial 3x2 (tres tipos de suplementación: sal mineral, MBs y MBs + heno buffel, y dos especies: borregos y cabritos) y 10 repeticiones. Los animales fueron criados en un sistema de pastoreo de pastizales en un área con vegetación característica del ecosistema de Caatinga bajo tres tipos de suplementación: 1: sal mineral solamente; 2: Bloques de alimentación (MBs); Y 3: MBs + heno buffel Se midió el peso, el rendimiento y los componentes de la mitad izquierda de la carcasa de corderos y cabritos. Resultados. Las cordeiros fueron superiores a las cabritos en conformación de carcasas, área de lomo, índice de musculatura de la pierna y índice de compacidad de la pierna mientras que las cabritos fueron superiores a las cordeiros en el peso de los músculos de las piernas. Conclusión. Cordeiros y cabritos, cuando se alimentan con suplementos de bloques de alimentación de pasto en el ecosistema de Caatinga; La suplementación con sal mineral y Bloques Multinutritivos con y sin Buffel puede ser utilizada para mejorar los rebaños en la caatinga, con resultados similares entre los tres. Las cordeiros muestran más adiposidad de carne que las cabritos, en contraste, las cabritos tienen mayor musculatura que las cordeiros cuando se alimentan con bloques de alimentación