NGHIÊN CỨU THIẾT LẬP CHUẨN ACID FENOFIBRIC

Abstract

Background: The fenofibric acid standard substance is a mandatory requirement in some analytical methods (such as HPLC, GC, LC_MS/MS) to check the quality of raw materials and finished products containing fenofibric acid, therefore, establishing a secondary standard of fenofibric acid is an urgent requirement in Vietnam. Objectives: To develop basic standards and establish a secondary standard for fenofibric acid which is synthesized in Vietnam. Materials and methods: Fenofibric acid is synthesized by hydrolysis of fenofibrate ester in the basic medium (NaOH) and purified by common methods. Product structure was determined by: IR, MS, ¹H-NMR, ¹³C-NMR, ¹H-¹H COSY, and XRD. Method for developing quality standards: Evaluation criteria are properties, pH, melting temperature, sulfate ash, weight loss due to drying, identification, impurities, and quantification. Tests are validated according to ICH, ASEAN guidelines, and specialized documents. Standard establishment method: The assigned value of the standard substance is calculated according to the formula: %Content (anhydrous) = Chromatographic purity × (100 - %inorganic impurities - %volatile impurities)/100. Results: Fenofibric acid was synthesized and purified from the hydrolysis reaction of fenofibrate ester with a yield of 96.22% (1.70g). IR, MS, ¹HNMR, ¹³C-NMR, ¹H-¹H COSY spectra all give signals consistent with the structure of the fenofibric acid molecule; the ultraviolet (UV) spectrum has a maximum absorption peak at 287.98 ± 2 nm. The material has a crystalline structure, with characteristic peaks (d, Å): 15.909; 18.401; 22.539; 23.059 (XRD spectrum). The tests were evaluated, the synthetic material met the established basic standards. The content (anhydrous) of the fenofibric acid secondary standard is 99.4 ± 0.1%. Conclusion: Fenofibric acid after synthesis and purification was used to establish the secondary standard with a labeled (anhydrous) content of 99.4 ± 0.1%.