The stability of caffeic acid phenethyl ester (CAPE) and its fluorinated derivative (FCAPE) in rat plasma and conditions preventing their degradation are reported. Reverse-phase high-pressure liquid chromatography (HPLC) using taxifolin as an internal standard was applied for the quantitative determination of CAPE and FCAPE in rat plasma extracted with ethyl acetate. The assay was validated over a linear range of 0.25-10 microg/mL plasma (r(2) > 0.9990, n = 3). No endogenous interferences were observed in the chromatographic region of interest. The limits of quantification and detection were set at 0.25 and 0.1 microg/mL, respectively. The precision ranged from 0.7 to 13.7% for CAPE, and from 0.4 to 10.4% for FCAPE. Accuracy ranged from -2.8 to 12.4% for CAPE and from -0.6 to 6.8% for FCAPE. The stability was conducted at 4, 25 and 37 degrees C. First-order kinetics was observed for the degradation of CAPE and FCAPE. The energies of activation of CAPE and FCAPE were found to be 17.9 and 20.1 kcal/mol, respectively. Addition of 0.4% of sodium chloride and pH adjustment to 6 prevented their degradation in rat plasma for 24 h and at least one month at -20 degrees C. This study provides useful information for the future pharmacokinetic study of CAPE and FCAPE in rat.