Bezafibrato: validação de metodologia e aplicação em estudo farmacocinético de formulações farmacêuticas

Abstract

Fibrates constitute an important class of drugs used in the treatment of the dyslipidemia, which is the main risk factor for the aterosclerosis development and incidence of cardiovascular diseases. The present dissertation reports the development and the validation of procedures for the bezafibrate (BEZ) analysis in pharmaceutical products and biological matrixes. The proposed methods include high performance liquid chromatography (HPLC) in reverse phase with ultraviolet detection (UV) and spectrophotometry with UV detection. For the chromatographic determination of bezafibrate in tablets, capsules and human plasma, were used a C-18 column (150 mm x 4.6 mm d.i, 5 μm), mobile phase composed by potassium phosphate buffer 0.01 M, pH 3.5: acetonitrile: methanol (50: 40: 10, v/v/v) with flow rate of 1 mL/min and detection at 230 nm. The extraction of the drug from the plasma was performed by liquid-liquid extraction using acidified tert-butyl methyl ether. For the spectrophotometric bezafibrate evaluation in tablets and capsules were used methanol and sodium hydroxide 0.1 N as solvents, with detection at 230 nm. The methodology developed for bezafibrate evaluation was validated observing the parameters specificity, linearity, precision, accuracy, recovery, robustness, stability and it was considered suitable for the analysis of the drug in formulations and biological fluids. The comparison of results demonstrated that there is not significant difference between the validated analytical methods (p<0.05). The bioanalytical developed method was applied with success for the determination of bezafibrate plasma in six healthy volunteers, allowing analysis of parameters as plasma maximum concentration (Cmax), extension of the absorption (AUC), constant of elimination (kel) and half-life time (t1/2).