Simultaneous Determination of Bufalin and Its Nine Metabolites in Rat Plasma for Characterization of Metabolic Profiles and Pharmacokinetic Study by LC-MS/MS

doi:10.3390/molecules24091662

	Simultaneous Determination of Bufalin and Its Nine Metabolites in Rat Plasma for Characterization of Metabolic Profiles and Pharmacokinetic Study by LC-MS/MS
	Wei, Wenlong; Yu, Yang; Wang, Xia; Yang, Linhui; Zhang, Hang; Ji, Hongjian; Li, Zhenwei; Hou, Jinjun; Wu, Wanying; Guo, Dean
刊名	MOLECULES
	2019-05-01
卷号	24 期号:9 页码:15
关键词	bufalin metabolite quantification pharmacokinetics
ISSN号	1420-3049
DOI	10.3390/molecules24091662
通讯作者	Wu, Wanying(wanyingwu@simm.ac.cn) ; Guo, Dean(daguo@simm.ac.cn)
英文摘要	Characterization and determination of metabolites to monitor metabolic pathways play a paramount role in evaluating the efficacy and safety of medicines. However, the separation and quantification of metabolites are rather difficult due to their limited contents in vivo, especially in the case of Chinese medicine, due to its complexity. In this study, an effective and convenient method was developed to simultaneously quantify bufalin and its nine metabolites (semi-quantitation) in rat plasma after an oral administration of 10 mg/kg to rats. The prototype and metabolites that were identified were subsequently quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 387.4369.6 and 387.4351.3 for bufalin, m/z 513.7145.3 for IS, and 387.4369.6, 419.2365.2, and 403.2349.2 for the main metabolites (3-epi-bufalin, dihydroxylated bufalin, and hydroxylated bufalin, respectively). The method was validated over the calibration curve range of 1.00-100 ng/mL with a limit of quantitation (LOQ) of 1 ng/mL for bufalin. No obvious matrix effect was observed, and the intra- and inter-day precisions, as well as accuracy, were all within the acceptable criteria in this method. Then, this method was successfully applied in metabolic profiling and a pharmacokinetic study of bufalin after an oral administration of 10 mg/kg to rats. The method of simultaneous determination of bufalin and its nine metabolites in rat plasma could be useful for pharmacokinetic-pharmacodynamic relationship research of bufalin, providing experimental evidence for explaining the occurrence of some adverse effects of Venenum Bufonis and its related preparations.
资助项目	National Natural Science Foundation of China[81530095] ; National Natural Science Foundation of China[81673591] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020348] ; National Standardization of Traditional Chinese Medicine Project[ZYBZH-K-LN-01] ; Science and Technology Commission Foundation of Shanghai[15DZ0502800]
WOS关键词	PERFORMANCE LIQUID-CHROMATOGRAPHY ; BUFADIENOLIDES ; MICROSOMES ; APOPTOSIS
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000469518100021
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289582]
专题	中国科学院上海药物研究所
通讯作者	Wu, Wanying; Guo, Dean
作者单位	Chinese Acad Sci, Shanghai Res Ctr Modernizat Tradit Chinese Med, Natl Engn Lab TCM Standardizat Technol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wei, Wenlong,Yu, Yang,Wang, Xia,et al. Simultaneous Determination of Bufalin and Its Nine Metabolites in Rat Plasma for Characterization of Metabolic Profiles and Pharmacokinetic Study by LC-MS/MS[J]. MOLECULES,2019,24(9):15.
APA	Wei, Wenlong.,Yu, Yang.,Wang, Xia.,Yang, Linhui.,Zhang, Hang.,...&Guo, Dean.(2019).Simultaneous Determination of Bufalin and Its Nine Metabolites in Rat Plasma for Characterization of Metabolic Profiles and Pharmacokinetic Study by LC-MS/MS.MOLECULES,24(9),15.
MLA	Wei, Wenlong,et al."Simultaneous Determination of Bufalin and Its Nine Metabolites in Rat Plasma for Characterization of Metabolic Profiles and Pharmacokinetic Study by LC-MS/MS".MOLECULES 24.9(2019):15.