Simultaneous determination of resibufogenin and its eight metabolites in rat plasma by LC-MS/MS for metabolic profiles and pharmacokinetic study
文献类型：期刊论文
| 作者 | Wei, Wen-long; An, Ya-ling; Li, Zhen-wei; Wang, Ying-ying; Ji, Hong-jian; Hou, Jin-jun ; Wu, Wan-ying; Guo, De-an
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| 刊名 | PHYTOMEDICINE
 |
| 出版日期 | 2019-07-01 |
| 卷号 | 60页码:7 |
| 关键词 | Resibufogenin Metabolites Quantitation Pharmacokinetics Metabolic profiles |
| ISSN号 | 0944-7113 |
| DOI | 10.1016/j.phymed.2019.152971 |
| 通讯作者 | Wu, Wan-ying(wangyingwu@simm.ac.cn) ; Guo, De-an(daguo@simm.ac.cn) |
| 英文摘要 | Background: Resibufogenin is one of the main active compounds of Venenum Bufonis and exhibits diverse pharmacological activities. It is brought into focus for its potency in heart failure and cancer therapy. Purpose: The purpose of this study was to establish a convenient and effective method which was used to simultaneously determine the resibufogenin and its metabolites in rat plasma for further understanding the metabolic profiles of resibufogenin in vivo and pharmacokinetic study by LC-MS/MS. Methods: The analytes were separated on a BEH C18 column with a mobile phase of water containing 0.05% formic acid and acetonitrile under gradient elution at a flow rate of 0.4 ml/min. Resibufogenin and its eight metabolites were quantified in positive electrospray ionization and MRM mode with transitions of m/z 385.5 -> 349.2 for resibufogenin; m/z 513.7 -> 145.3 for IS (internal standard); m/z 401.23 -> 365.21, m/z 417.23 -> 285.21 and m/z 385.24 -> 349.21 for three main metabolites (hydroxylated-resibufogenin; dihydroxylated-resibufogenin and 3-epi-resibufogenin, respectively). Results: This method was successfully validated with a good linearity over the concentration ranges of 1-200 ng/ml for resibufogenin and the correlation coefficients was more than 0.990. The lower limit of quantification was 1 ng/ml and the precision and accuracy values were less than 15%. The method was applied to study the metabolic profiles of resibufogenin in rat plasma after oral administration of 20 mg/kg. The results indicated that the metabolic reactions of resibufogenin were mainly hydroxylation, dihydroxylation, dehydrogenation and isomerization. Totally eleven metabolites were identified, among which eight were successfully quantified. Conclusion: The results could provide further research foundation for the mechanisms study of activity and toxicity in vivo and facilitate the appropriate clinical application of resibufogenin. |
| WOS关键词 | CYTOTOXIC BUFADIENOLIDES ; LIQUID-CHROMATOGRAPHY ; CHINESE MEDICINE ; CINOBUFAGIN ; BIOTRANSFORMATION ; CYCLODEXTRIN ; SEPARATION ; CHANSU ; CELLS |
| 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研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000485781500014 |
| 出版者 | ELSEVIER GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/288828]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wu, Wan-ying; Guo, De-an |
| 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, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wei, Wen-long,An, Ya-ling,Li, Zhen-wei,et al. Simultaneous determination of resibufogenin and its eight metabolites in rat plasma by LC-MS/MS for metabolic profiles and pharmacokinetic study[J]. PHYTOMEDICINE,2019,60:7. |
| APA | Wei, Wen-long.,An, Ya-ling.,Li, Zhen-wei.,Wang, Ying-ying.,Ji, Hong-jian.,...&Guo, De-an.(2019).Simultaneous determination of resibufogenin and its eight metabolites in rat plasma by LC-MS/MS for metabolic profiles and pharmacokinetic study.PHYTOMEDICINE,60,7. |
| MLA | Wei, Wen-long,et al."Simultaneous determination of resibufogenin and its eight metabolites in rat plasma by LC-MS/MS for metabolic profiles and pharmacokinetic study".PHYTOMEDICINE 60(2019):7. |
入库方式： OAI收割
来源：上海药物研究所
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