ABSTRACT
Abstract A stability-indicating HPLC-DAD method was developed and validated for the simultaneous determination of dasabuvir and its degradation products in the pharmaceutical formulation. The proposed method utilized a Symmetry® C18 (4.6 x 75 mm, 3.5 µm) column, and the mobile phase consisted of an isocratic elution of formic acid (0.1%) and acetonitrile (55:45, v/v), at a flow of 1 mL min-1; analytes were detected at 244 nm. Dasabuvir was submitted to different stress degradation conditions, such as acidic, alkaline, neutral, thermal, oxidative and photolytic, and the structural elucidation of degradation products was performed using LC-QToF-MS/MS. The HPLC-DAD stability-indicating method was validated for selectivity, linearity, limit of detection and quantification, accuracy, precision and robustness, according to ICH guidelines. Dasabuvir produced two degradation products (DP1 and DP2) from the alkaline stress conditions, which were characterized in negative ion mode. Dasabuvir was linear in the range 9.78 to 136.92 µg mL-1, and DP and DP were linear in the range 2.9 to 20.2 µg mL-1 and 1.3 to 14.9 µg mL-1, respectively. The 1 2 recovery ranged between 99.16 and 100.86%, while precision ranged from 1.02 to 2.89%. As the method can effectively separate the dasabuvir from its degradation products and quantitate them, it may be employed as a stability-indicating method for the pharmaceutical formulation.
Subject(s)
Chromatography, High Pressure Liquid/methods , Drug Compounding/classificationABSTRACT
Objective: The Antimicrobial Stewardship Program (ASP) in hospitals aims to promote the rational use of antimicrobials, providing better results to patients (increasing effectiveness and decreasing the risk of adverse events), hospital epidemiology (impact on levels of microbial resistance), and enable cost-effectiveness studies. Therefore, a tool (called PRAT antimicrobial therapy-related problem) is suggested in this paper. This unvalidated tool is the initial step towards organizing the antimicrobial therapy-related interventions to improve the use of this drug class, mainly by suggesting a harmonized registry process of ASP interventions. Methods: Therefore, this work presents the PRAT tool, developed based on the 10 years' experience of ASP at Pequeno Príncipe Hospital, inspired by the classification for drug-related problems of the Pharmaceutical Care Network Europe and according to a collaborative work using the Delphi technique. Results: This tool allows the identification and exact description of the antimicrobial therapy-related problem in 17 domains and 67 subcategories. Based on this identification, it suggests how to classify this problem (effectiveness, safety and need/indication) and what interventions can be conducted. Conclusion: This tool has the potential to establish a profile of antimicrobial-related problems, allowing prioritization to be visualized through the most (and least) interventions made in a given period, and might be useful in improving the quality of care through settings, by means of targeted educational interventions. Furthermore, if there is a harmonization of terminology for the classification of antimicrobial therapy-related problems, other hospitals can adopt it, and so the tool can improve research and comparison between institutions (benchmarking).
ABSTRACT
Abstract We investigated the predictors of delay in the diagnosis and mortality of patients with COVID-19 in Rio de Janeiro, Brazil. A cohort of 3,656 patients were evaluated (Feb-Apr 2020) and patients' sociodemographic characteristics, and social development index (SDI) were used as determinant factors of diagnosis delays and mortality. Kaplan-Meier survival analyses, time-dependent Cox regression models, and multivariate logistic regression analyses were conducted. The median time from symptoms onset to diagnosis was eight days (interquartile range [IQR] 7.23-8.99 days). Half of the patients recovered during the evaluated period, and 8.3% died. Mortality rates were higher in men. Delays in diagnosis were associated with male gender (p = 0.015) and patients living in low SDI areas (p < 0.001). The age groups statistically associated with death were: 70-79 years, 80-89 years, and 90-99 years. Delays to diagnosis greater than eight days were also risk factors for death. Delays in diagnosis and risk factors for death from COVID-19 were associated with male gender, age under 60 years, and patients living in regions with lower SDI. Delays superior to eight days to diagnosis increased mortality rates.
Resumo Investigamos os preditores de atraso no diagnóstico e mortalidade de pacientes com COVID-19 no Rio de Janeiro, Brasil. Uma coorte de 3.656 pacientes foi avaliada (fevereiro-abril de 2020) e as características sociodemográficas dos pacientes, o bairro e o índice de desenvolvimento social (IDS) foram usados como fatores determinantes dos atrasos no diagnóstico e da mortalidade. Foram realizadas análises de sobrevivência de Kaplan-Meier, modelos de regressão Cox dependentes do tempo e análises de regressão logística multivariada. O tempo mediano desde o início dos sintomas até o diagnóstico foi de oito dias (intervalo interquartil [IQR] 7,23-8,99 dias). Metade dos pacientes se recuperou no período avaliado e 8,3% faleceram. As taxas de mortalidade foram maiores nos homens. Atrasos no diagnóstico foram associados ao sexo masculino (p = 0,015) e pacientes que moravam em áreas com baixo IDS (p < 0,001). As faixas etárias estatisticamente associadas à morte foram: 70-79 anos, 80-89 anos e 90-99 anos. Atrasos no diagnóstico superiores a oito dias também foram fatores de risco para óbito. Atrasos no diagnóstico e fatores de risco para morte por COVID-19 foram associados ao sexo masculino, idade abaixo de 60 anos e pacientes que vivem em regiões com menor IDS. Atrasos superiores a oito dias no diagnóstico aumentam as taxas de mortalidade.