The in vivo and in vitro metabolites of Worenine in rat were identified or characterized using a specific and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.
METHODS AND RESULTS:
In vivo samples including rat urine, feces, and plasma samples were collected after ingestion of 25 mg/kg Worenine to healthy rats. The in vivo and in vitro samples were cleaned up by a solid-phase extraction procedure (C18 cartridges) and a liquid-liquid extraction procedure, respectively. Then these pretreated samples were injected into a reversed-phase C18 column with mobile phase of methanol-ammonium acetate (2mM, adjusted to pH 3.5 with formic acid) (60:40, v/v) and detected by an on-line MS/MS system. As a result, at least twenty-seven metabolites and the parent medicine were found in rat urine after ingestion of Worenine. Seven metabolites and the parent medicine were identified or characterized in rat feces. Three metabolites and the parent medicine were detected in rat plasma. One metabolite was found in the rat intestinal flora incubation mixture, and three metabolites were characterized in the homogenized liver incubation mixture.
CONCLUSIONS:
The main phase I metabolism of Worenine in rat was dehydrogenization, hydrogenation, hydroxylation, and demethylene reactions, and that of phase II was sulfation and glucuronidation. |
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