Development of a high-perofrmance liquid chroatographic method for bioequivalence study of flavoxate tablets

摘要

An improved HPLC method was developed for the concentration determination of the metabolite of flavoxate, 3-methyl-flavone-8-carboxylic acid (MFCA), in plasma in an attempt to compare two flavoxate tablet formulations. This HPLC method was validated by examining the precision and the accuracy for inter-day and intra-day runs in a linear concentration range of 0.1—24 jig/mI. The coefficients of variation (CV) of inter-day and intra-day assays were 0.24—7.18% and 0.06—5.70%, respectively. The standard errors of mean (S.E.M.) were —0.004—8.68% and —2.52—4.86% for inter-day and intra-day assays, respectively. Bioequivalence of the two formulations was determined on 12 normal healthy male volunteers in a single-dose, two-period, two-sequence. two-treatment crossover study. MFCA plasma concentrations were analyzed with this validated HPLC method. The normal pivotal parameters, AUCOIa~t~ AUC0,~f and C max’ were calculated and compared using the SAS General Linear Model computer program. The two one-sided t distribution test was also performed, as well as the 90% confidence-interval method, for the mean difference of the three pivotal parameters. The results suggest that these two flavoxate tablet formulations are non-bioequivalent when orally administered in a 400-mg dose of two tablets. This result was consistent with the in vitro dissolution of these two formulations.