New analytical method for the study of the metabolism of gentiopicroside in rats after oral administration by LC-TOF-MS following picolinoyl derivatization.

The metabolism of gentiopicroside (GPS) in vivo was studied for the first time by LC-MS following picolinoyl derivatization. Incubation of erythrocentaurin, one of the main in vitro metabolites of GPS by intestinal bacteria, with liver microsome indicated that GPS might be metabolized to a final metabolite 3,4-dihydro-5-(hydroxymethyl)isochroman-1-one (HMIO) in vivo. After hydrolysis with sulfatase, HMIO was successfully detected in rat plasma after oral administration of GPS by LC-MS following picolinoyl derivatization. 4-Methoxyphenyl methanol was used as an internal standard to quantify HMIO in rat plasma. A metabolic pathway of GPS in rats is proposed. The monoterpene compound GPS was found to be metabolized to dihydroisocoumarin, which may be responsible for the pharmacological effect of GPS.