Metabolism of eupatilin in rats using liquid chromatography/electrospray mass spectrometry

Eupatilin (5,7-dihydroxy-3′,4′,6-trimethoxyflavone) is an active ingredient of an ethanol extract of Artemisia asiatica (DA-9601) that is used in the treatment of gastritis. In vitro and in vivo metabolism of eupatilin in the rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of eupatilin in the presence of NADPH and UDPGA resulted in the formation of four metabolites (M1-M4). M1, M2, M3 and M4 were tentatively identified as 3′- or 4′-O-demethyleupatilin glucuronide, eupatilin glucuronide, 6-O-demethyleupatilin and 3′- or 4′-O-demethyl-eupatilin, respectively. Those metabolites from in vitro study were also characterized in bile, plasma or urine samples after an intravenous administration of eupatilin to rats. In rat bile, plasma and urine samples, eupatilin glucuronide (M2) was a major metabolite, whereas M3, M4 and M4 glucuronide (M1) were the minor metabolites.