Simultaneous determination of cinobufagin and its five metabolites in rat plasma by LC-MS/MS for characterization of metabolic profiles and pharmacokinetic study

doi:10.1039/c9ay00807a

	Simultaneous determination of cinobufagin and its five metabolites in rat plasma by LC-MS/MS for characterization of metabolic profiles and pharmacokinetic study
	Wei, Wenlong; Li, Haojv; Li, Zhenwei; Qu, Hua; Da, Juan; Jin, Xu; Wang, Yingying; Wu, Wanying; Guo, De-an
刊名	ANALYTICAL METHODS
	2019-11-14
卷号	11 期号:42 页码:5464-5471
ISSN号	1759-9660
DOI	10.1039/c9ay00807a
通讯作者	Wu, Wanying(wanyingwu@simm.ac.cm) ; Guo, De-an(daguo@simm.ac.cn)
英文摘要	Cinobufagin is one of the main ingredients of Venenum Bufonis and has various pharmacological activities and toxicities. It is very important to simultaneously determine cinobufagin and its metabolites because of its strong physiological activity but it is also very challenging due to its low concentration in blood. In this study, a convenient and efficient method was developed to simultaneously determine cinobufagin and its five metabolites in rat plasma (semi-quantification). BF211, the derivative of bufalin, was added to the plasma sample as an internal standard (IS). An ACQUITY BEH C18 column (2.1 mm x 50 mm, 1.7 mu m) was used for the separation at 40 degrees C, and the mobile phase containing the acetonitrile and water added 0.05% formic acid was run under gradient elution at 0.4 mL min(-1). A LC-MS/MS with an electrospray ionization source in positive ion mode was used for the quantification of cinobufagin and its five metabolites in the mode of multiple reaction monitoring (MRM). The monitored ion pairs were m/z 443.5 -> 365.3 for the transition of cinobufagin, m/z 513.7 -> 145.3 for IS, and m/z 443.2 -> 365.2, 401.2 -> 265.2, and 417.2 -> 363.2 for 3-epi-cinobufagin, desacetylcinobufagin and hydroxyl-desacetylcinobufagin respectively. The calibration curve of cinobufagin showed good linearity in the range of 1.0-200 ng mL(-1) (y = 0.201x + 0.105 and R-2 > 0.990) and the limit of quantitation (LOQ) was 1.0 ng mL(-1). The specificity, accuracy, precision, extraction recovery, matrix effect and stability of the method were satisfactory. According to the results of pharmacokinetic study, cinobufagin was absorbed quickly (T-max = 0.083 +/- 0 h) and the main metabolite was desacetylcinobufagin (C-max = 897.95 +/- 237.35 ng mL(-1)). This pharmacokinetic study could be used for obtaining essential data to interpret the pharmacokinetic-pharmacodynamic relationships of cinobufagin.
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 ; TRADITIONAL CHINESE MEDICINE ; SHEXIANG BAOXIN PILL ; LIU-SHEN-WAN ; CHAN-SU ; BUFADIENOLIDES ; IDENTIFICATION ; PURIFICATION ; KYUSHIN ; PLANT
WOS研究方向	Chemistry ; Food Science & Technology ; Spectroscopy
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000493548400012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281780]
专题	中国科学院上海药物研究所
通讯作者	Wu, Wanying; Guo, De-an
作者单位	Chinese Acad Sci, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai Inst Mat Med, Natl Engn Lab TCM Standardizat Technol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wei, Wenlong,Li, Haojv,Li, Zhenwei,et al. Simultaneous determination of cinobufagin and its five metabolites in rat plasma by LC-MS/MS for characterization of metabolic profiles and pharmacokinetic study[J]. ANALYTICAL METHODS,2019,11(42):5464-5471.
APA	Wei, Wenlong.,Li, Haojv.,Li, Zhenwei.,Qu, Hua.,Da, Juan.,...&Guo, De-an.(2019).Simultaneous determination of cinobufagin and its five metabolites in rat plasma by LC-MS/MS for characterization of metabolic profiles and pharmacokinetic study.ANALYTICAL METHODS,11(42),5464-5471.
MLA	Wei, Wenlong,et al."Simultaneous determination of cinobufagin and its five metabolites in rat plasma by LC-MS/MS for characterization of metabolic profiles and pharmacokinetic study".ANALYTICAL METHODS 11.42(2019):5464-5471.