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.

Keywords:

• 6-O-methyl-scutellarein
• metabolic stability
• scutellarin
• UFLC/Q-TOF/MS

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding information

This work was supported by National Natural Science Foundation of China (No. 81274058), the Program for New Century Excellent Talents by the Ministry of Education (NCET-12-0741), 333 High-level Talents Training Project Funded by Jiangsu Province, Six Talents Project Funded by Jiangsu Province (2013-YY-010), Technology Innovation Venture Fund by Nanjing University of Chinese Medicine (CX201301), Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (ysxk-2010), Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions and Project Funded by the Flagship Major Development of Jiangsu Higher Education Institutions (PPZY2015A070) and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (ZDXMHT-1-13).