Abstract: To study the pharmacokinetic characteristic of antitumorcaffeic acid-3,4-dihydroxybenzylethyl(3,4-dihydroxyphenethyl)ester(CADPE) in human liver microsomes.Human liver microsomes were incubated in vitro with CADPE for different times. LC-MS method was applied to determine the concentrations of CADPE and its metabolites of hydroxytyrosol and caffeic acid at the designed time points. An LC-MS analytic method was established and validated to determine the concentrations of CADPE and its metabolites hydroxytyrosol and caffeic acid inhuman liver microsomes. CADPE metabolism showed single compartment model and its half-life(T_1/2) was 0.72±0.09 h. The time to peak(Tmax) and the half-life(T_1/2) for hydroxytyrosol was 1.3±0.3 h,3.97±0.58 h,respectively. Hydroxytyrosol metabolism showed single compartment characteristic. The relationship of caffeic acid concentration and time was logarithmic.The concentration of caffeic acid gradually increased and finally reached steady state with the gradual metabolism of CADPE. This study clarified the pharmacokinetic characteristics of CADPE and its metabolites hydroxytyrosol and caffeic acid in human liver microsomes. The data obtained also provided scientific basis for the further investigation of the pharmacokinetic characteristics of CADPE in animals and human.

Key words: LC-MS, CADPE, human liver microsomes, pharmacokinetics, hydroxytyrosol, caffeic acid