title: Two main metabolites of gentiopicroside detected in rat plasma by LC-TOF-MS following 2,4-dinitrophenylhydrazine derivatization.
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.
authors.affiliation: National TCM Key Lab 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. Electronic address: wangzhigang0513@vip.163.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
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: 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 Lab 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: Ning
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D057888:Iridoid Glucosides / Q000097:blood* / Q000737:chemistry* / Q000378:metabolism; D039823:Iridoids / Q000737:chemistry; D049934:Isocoumarins / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D010659:Phenylhydrazines / Q000737:chemistry* / Q000378:metabolism; D010949:Plasma / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D057888:Iridoid Glucosides; D039823:Iridoids; D049934:Isocoumarins; D010659:Phenylhydrazines; C012997:gentiopicroside; C004787:2,4-dinitrophenylhydrazine; C007623:erythrocentaurin
keywords: Erythrocentaurin; Gentiopicral; Gentiopicroside; Metabolism