Determination of a astragaloside IV derivative LS-102 in plasma by ultra-performance liquid chromatography-tandem mass spectrometry in dog plasma and its application in a pharmacokinetic study

doi:10.1016/j.phymed.2018.09.019

CORC > 成都生物研究所 > 中国科学院成都生物研究所 > 国家天然药物工程技术研究中心 > 天然产物研究

	Determination of a astragaloside IV derivative LS-102 in plasma by ultra-performance liquid chromatography-tandem mass spectrometry in dog plasma and its application in a pharmacokinetic study
	Sun Wen-Xia 2,3,4; Zhang Zhi-Feng 3; Xie Jing 1,3; He Ying 2; Cheng Yong 2; Ding Li-Sheng 4; Luo Pei 3; Qing Lin-Sen 4
刊名	PHYTOMEDICINE
	2019
卷号	53 页码:243-251
关键词	Astragalosidic acid Astragaloside IV derivative Pharmacokinetics Bioavailability UPLC-MS/MS
ISSN号	0944-7113
DOI	10.1016/j.phymed.2018.09.019
产权排序	1
文献子类	Article
英文摘要	Background: Astragalosidic acid (LS-102) is a new water-soluble derivative of astragaloside IV - a major effective component isolated from the Chinese herb Astragali Radix. Our previous study showed that LS-102 exhibited potent cardiovascular activity. Purpose: The objective of this study was to investigate the pharmacokinetic properties of LS-102 after single-dose, oral administration in beagle dogs by developing and validating an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Method and result: The chromatographic separation was performed on a Acquity HSS C-18 column (100 mm x 2.1 mm, 1.8 mu m) by a gradient elution using a mobile phase consisting of water and acetonitrile at a flow rate of 0.35 ml/min. The analytes were detected with a triple quadrupole tandem mass spectrometry in multiple reaction monitoring mode. Method validation revealed a wide linearity over the range of 2.0-10,000 ng/ml together with satisfactory intra- and inter-day precision, accuracy, and recovery. Stability testing showed that LS-102 spiked into dog plasma was stable for 4 h at room temperature, for up to 2 weeks at -80 degrees C, and during three freeze-thaw cycles. The method was effectively and successfully applied to the pharmacokinetics of LS-102 after oral administration (5, 10 and 20 mg/kg) to beagle dogs. Peak plasma concentrations are attained within approximately 2 h after oral administration with a half-life ranging from 1.55 h to 4.49 h. The plasma concentration-time curve of LS-102 after oral administration presents the phenomenon of a double-peak absorption phase. The peak concentration and area under the concentration-time curve of LS-102 seemed to increase with the increasing doses proportionally, that suggesting linear pharmacokinetics in dogs. Meanwhile, the doxorubicin (Dox)-injured H9c2 cell model was prepared by incubating the cells in 1 mu M Dox for 24 h. MTT assay and LDH release measurement showed that LS-102 protected against Dox-induced cardio-myocyte death. Conclusion: The obtained results may help to guide the further pre-clinical research of LS-102 as a potentially novel cardioprotective agent.
学科主题	Pharmacology & Toxicology
URL标识	查看原文
WOS关键词	TRANSPORT ; RADIX
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种	英语
出版者	ELSEVIER GMBH
WOS记录号	WOS:000459935700026
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/31083]
专题	国家天然药物工程技术研究中心_天然产物研究
作者单位	1.Chengdu Med Coll, Sch Pharm, Chengdu, Sichuan, Peoples R China 2.Chengdu Univ, Sichuan Ind Inst Antibiot, Chengdu, Sichuan, Peoples R China; 3.Macau Univ Sci & Technol, State Key Labs Qual Res Chinese Med, Macau, Peoples R China; 4.Chinese Acad Sci, Chengdu Inst Biol, 4-9 South Renmin Rd, Chengdu, Sichuan, Peoples R China;
推荐引用方式 GB/T 7714	Sun Wen-Xia,Zhang Zhi-Feng,Xie Jing,et al. Determination of a astragaloside IV derivative LS-102 in plasma by ultra-performance liquid chromatography-tandem mass spectrometry in dog plasma and its application in a pharmacokinetic study[J]. PHYTOMEDICINE,2019,53:243-251.
APA	Sun Wen-Xia.,Zhang Zhi-Feng.,Xie Jing.,He Ying.,Cheng Yong.,...&Qing Lin-Sen.(2019).Determination of a astragaloside IV derivative LS-102 in plasma by ultra-performance liquid chromatography-tandem mass spectrometry in dog plasma and its application in a pharmacokinetic study.PHYTOMEDICINE,53,243-251.
MLA	Sun Wen-Xia,et al."Determination of a astragaloside IV derivative LS-102 in plasma by ultra-performance liquid chromatography-tandem mass spectrometry in dog plasma and its application in a pharmacokinetic study".PHYTOMEDICINE 53(2019):243-251.