title: New analytical method for the study of metabolism of swertiamarin in rats after oral administration by UPLC-TOF-MS following DNPH derivatization.
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.
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.|Harbin Children Hospital, Youyi road 57, Harbin, China.
authors.forename: Shuhan
authors.initials: S
authors.lastname: Tang
authors.affiliation: Harbin Children Hospital, Youyi road 57, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Harbin Children Hospital, Youyi road 57, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Hattori
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China.
authors.forename: Xijun
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Shaanxi, 710061, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China.|Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D057888:Iridoid Glucosides / Q000008:administration & dosage / Q000032:analysis / Q000097:blood* / Q000378:metabolism*; D049934:Isocoumarins / Q000032:analysis / Q000097:blood / Q000378:metabolism; D057230:Limit of Detection; D053858:Metabolic Networks and Pathways; D010659:Phenylhydrazines / Q000737:chemistry; D011753:Pyrones / Q000008:administration & dosage / Q000032:analysis / Q000097:blood* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D029967:Swertia / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D057888:Iridoid Glucosides; D049934:Isocoumarins; D010659:Phenylhydrazines; D011753:Pyrones; C004787:2,4-dinitrophenylhydrazine; C007623:erythrocentaurin; C013270:swertiamarin
keywords: derivatization; erythrocentaurin; metabolism; swertiamarin