Desenvolvimento e validação de método indicativo de estabilidade para quantificação de secnidazol e compostos relacionados por cromatografia líquida de alta eficiência

Abstract

In 2017, 4,757 deaths due to acute diarrheal disease (ADD) were reported in Brazil, which representes a mortality rate of 2.3 x 100,000 inhabitants. Among the main etiological agents of ADD is the protozoan Giardia duodenalis, both in developing and developed countries. Giardiasis usually causes diarrhea and, even in the absence of apparent clinical manifestations, it is related to no absorption of nutrient and growth deficiencies, especially in children under 10 years of age. Among the treatments suggested by the Ministry of health is the oral administration of the antiparasitic secnidazole (SCZ), which, despite being an important Active pharmaceutical ingredient for the treatment of giardiasis, and other negligible diseases, does not have an analysis methodology described in the Brazilian Pharmacopoeia or in other compendiums interchangeable. The resolution that establishes parameters for the notification, identification, and qualification of degradation products in medicines with synthetic active substances is RDC nº 53, December 4th, 2015. For the active pharmaceutical ingredients classified as synthetic and semi-synthetic, ANVISA expects that they are qualified according to the parameters defined by RDC No. 53/2015 but following the qualification limits established by the ICH Q3A (R2) guide, until the specific legislation comes into force. Simultaneously with the publication of RDC No. 53/2015, Guide No. 4 was also published, which deals with obtaining the degradation profile, and identification and qualification of degradation products in medicines, which brought further clarification on how to proceed during a forced degradation study, as well as its importance for the development of an indicative method of stability. Therefore, the objective of the present work was to develop and validate a method indicative of stability capable of quantifying the antiparasitic secnidazole and its related compounds by high performance chromatography. For the optimized conditions, a Symmetry C8 column (250 x 4.6 mm, 5μm) is used as a stationary phase, as a mobile phase: methanol: water (20: 80 v / v), flow of 1.0 m / min, and 319 nm as the detection wavelength. The results obtained show that the analytical methodology is precise, exact, robust, and linear in the concentration range 400 to 600 μg / mL of SCZ. It was also shown to be precise, accurate, robust, and linear in the concentration range 0.50 to 1.80 μg / mL for the impurities of SCZ synthesis. During the degradation study, the SCZ was mainly susceptible to basic hydrolysis, presenting degradation products of m/z 606 and 321, respectively.