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Two main metabolites of gentiopicroside detected in rat plasma by LC-TOF-MS following 2,4-dinitrophenylhydrazine derivatization.

Journal of pharmaceutical and biomedical analysis (2015-01-06)
Zhigang Wang, Shuhan Tang, Yan Jin, Yan Zhang, Masao Hattori, Hailong Zhang, Ning Zhang
ABSTRACT

The metabolism of gentiopicroside in vivo was studied by LC/MS following 2,4-dinitrophenylhydrazine derivatization for the first time. The ionization efficiency of the major metabolites erythrocentaurin and gentiopicral were greatly enhanced by the new analytical method developed, and they were successfully detected in rat plasma after oral administration of gentiopicroside. Methyl 4-formylbenzoate was used as the internal standard to quantify erythrocentaurin and gentiopicral in rat plasma in negative mode by UPLC-TOF-MS. It was found that erythrocentaurin reached the maximum plasma concentration of 625.2±246.3 ng/mL at about 2 h and gentiopicral reached the maximum plasma concentration of 157.6±86.6 ng/mL at about 4 h after oral administration of gentiopicroside at a dose of 200 mg/kg. The metabolic pathway of gentiopicroside to erythrocentaurin and gentiopicral was proposed. The monoterpene compound gentiopicroside was found to be metabolized to dihydroisocoumarin in vivo which may be responsible for the pharmacological effect of gentiopicroside. The results may shed light on clinical efficacy of gentiopicroside and the new analytical method developed may assist in studies for the metabolism of other natural iridoids and secoiridoids in vivo.

MATERIALS
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Product Description

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