title: Investigation of 6-O-methyl-scutellarein metabolites in rats by ultra-flow liquid chromatography/quadrupole-time-of-flight mass spectrometry.
abstract: Context Scutellarin (1) has been widely used in China to treat acute cerebral infarction and paralysis induced by cerebrovascular diseases. However, scutellarin (1) has unstable metabolic characteristics. Objective The metabolic profile of 6-O-scutellarein was studied to determine its metabolic stability in vivo. Materials and methods In this study, a method of UFLC/Q-TOF MS was used to study the 6-O-methyl-scutellarein metabolites in rat plasma, urine, bile and faeces after oral administration of 6-O-methyl-scutellarein (3). One hour after oral administration of 6-O-methyl-scutellarein (3) (34 mg/kg), approximately 1 mL blood samples were collected in EP tubes from all groups. Bile, urine and faeces samples were collected from eight SD rats during 0-24 h after oral administration. The mass defect filtering, dynamic background subtraction and information dependent acquisition techniques were also used to identify the 6-O-methyl-scutellarein metabolites. Results The parent compound 6-O-methyl-scutellarein (3) was found in rat urine, plasma, bile and faeces. The glucuronide conjugate of 6-O-methyl-scutellarein (M1, M2), diglucuronide conjugate of 6-O-methyl-scutellarein (M3), sulphate conjugate of 6-O-methyl-scutellarein (M4), glucuronide and sulphate conjugate of 6-O-methyl-scutellarein (M5), methylated conjugate of 6-O-methyl-scutellarein (M6) were detected in rat urine. M1, M2 and M3 were detected in rat bile. M1 was found in rat plasma and M7 was detected in faeces. Discussion and conclusion Because the parent compound 6-O-methyl-scutellarein (3) was found in rat urine, plasma, bile and faeces, we speculate that 6-O-methyl-scutellarein (3) had good metabolic stability in vivo. This warrants further study to develop it as a promising candidate for the treatment of ischemic cerebrovascular disease.
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
authors.forename: Nian-Guang
authors.initials: NG
authors.lastname: Li
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
authors.forename: Ze-Xi
authors.initials: ZX
authors.lastname: Dong
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
authors.forename: Ting
authors.initials: T
authors.lastname: Gu
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Wu
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
authors.forename: Peng-Xuan
authors.initials: PX
authors.lastname: Zhang
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
authors.forename: Shao-Peng
authors.initials: SP
authors.lastname: Yu
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
authors.affiliation: b Department of Organic Chemistry , China Pharmaceutical University , Nanjing , P.R. China.
authors.forename: Zhi-Hao
authors.initials: ZH
authors.lastname: Shi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D047309:Flavones / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000652:urine; D020719:Glucuronides / Q000378:metabolism; D008297:Male; D050217:Metabolic Detoxication, Phase II; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: C000603945:6-O-methylscutellarein; D004365:Drugs, Chinese Herbal; D047309:Flavones; D020719:Glucuronides; D013431:Sulfates
keywords: 6-O-methyl-scutellarein; UFLC/Q-TOF/MS; metabolic stability; scutellarin