Dissertação
Bezafibrato: validação de metodologia e aplicação em estudo farmacocinético de formulações farmacêuticas
Fecha
2007-10-11Registro en:
MELO, Janine de. BEZAFIBRATE: VALIDATION OF METHODOLOGY AND
APPLICATION IN PHARMACOKINETIC STUDY
OF PHARMACEUTICAL FORMULATIONS. 2007. 127 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2007.
Autor
Melo, Janine de
Institución
Resumen
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).