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New analytical method for the study of metabolism of swertiamarin in rats after oral administration by UPLC-TOF-MS following DNPH derivatization.

Biomedical chromatography : BMC (2015-01-23)
Xiuhong Wu, Shuhan Tang, Yan Jin, Yan Zhang, Masao Hattori, Xijun Wang, Hailong Zhang, Zhigang Wang
ABSTRACT

The metabolism of swertiamarin in vivo was studied by LC-MS following 2,4-dinitrophenylhydrazine derivatization. The ionization efficiency of the main metabolite erythrocentaurin was greatly enhanced by the new analytical method developed, and erythrocentaurin was successfully detected for the first time in rat plasma after oral administration of swertiamarin. Methyl 4-formylbenzoate was used as the internal standard to quantify erythrocentaurin in rat plasma in negative mode by UPLC-TOF-MS, and it was found that erythrocentaurin reached the maximum mean plasma concentration of 425.8 ± 127.6 ng/mL at about 2 h after oral administration of swertiamarin at a dose of 200 mg/kg. A metabolic pathway of swertiamarin to erythrocentaurin was proposed. Swertiamarin is first hydrolyzed by bacterial β-glucusidase to give the aglycone, which is readily converted to erythrocentaurin. The monoterpene compound swertiamarin was found to be metabolized to dihydroisocoumarin and alkaloid compounds in vivo, which may be responsible for the pharmacological effect of swertiamarin. The results may shed light on the clinical efficacy of swertiamarin and the new analytical method may assist in studies for the metabolism of other natural iridoids and secoiridoids in vivo.

MATERIALS
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