Desenvolvimento e validação de metodologia analítica verde para quantificação de ácido acetilsalícilico em formulações farmacêuticas

Abstract

Themes of sustainability and productivity are increasingly on the rise, due to the constant increase in demands and global guidelines leading to an increasingly sustainable world, always considering the gain of time. In the pharmaceutical field, these themes are also present, requiring methodologies increasingly faster, less toxic and less harmful to the environment. Given this scenario, one of the drugs with the highest production and consumption worldwide is Aspirin®, one of the oldest drugs in the pharmaceutical market. With its high-volume production and high consumption, consequently large volumes of analyses, high solvent expenditure and time required for such analyses, it is necessary and important to develop more agile methodologies and with less use of solvents. In addition to the reduction in the use of organics, the acetonitrile crisis that has been going on for some years is well known, having intensified in the last year and continued in the current year. Therefore, it is also important to work with methodologies that reduce or eliminate the use of acetonitrile as a solvent, eliminating the risk of compromising the analyzes due to the lack of this solvent. Thus, the analytical methodology was developed with a Chromolith High Resolution RP-18 100mm x 4.6mm monolithic block column, with 2 mL.min-1 of flow in a composition of 38% ethanol and 62% acidified water phosphoric acid, temperature 30°C, 10 μL injection volume in a run time of 3.5 minutes. For validation, selectivity, linearity, precision, accuracy, detection limits and quantification tests were performed. The selectivity presented results within acceptable standards, using Parteck® SI 200 as placebo, since there was no interference in the same retention time of acetylsalicylic acid. The calibration curve was linear, with a correlation coefficient greater than 0.99. Precision tests were evaluated by repeatability and reproducibility, which showed coefficients of variation of 0.36% and 0.55%, respectively. The accuracy also presented results within the acceptance criteria stipulated by RDC No. 166/2017, where recovery was evaluated at 80, 100 and 120% (400, 500 and 600 mg/tablet). Limits of detection and quantification were also evaluated, presenting values of 0.04 mg.mL-1 and 0.52 mg.mL-1. Therefore, the developed method can be successfully applied to Aspirin® tablet content analysis. In addition, the methodology developed was measured for green character, being evaluated by four metrics: green star, NEMI, AGREE, analytical echo scale and cost and time analysis. By the green star, the methodology developed meets the 5 principles of Green Chemistry against the 2 principles met by the pharmacopeial methodology. By NEMI, 3 filled quadrants compared to 2 quadrants of the original method and a score of 93 on the analytical echo scale compared to 80 points of the pharmacopeia. According to AGREE, the green methodology presented a score of 0.67 versus 0.35 of the original method, also proving the greater green character of the developed methodology. In addition, it presented a 72.5% reduction (from R$51.78 to R$14.24 considering 15 runs) in cost and 65% in time (from 10 minutes to 3.5 minutes) in relation to the pharmacopeial methodology.