高效液相色谱-三重四极杆/线性离子阱质谱法研究大鼠口服不同剂量广金钱草总黄酮后的药动学特征

doi:10.11669/cpj.2021.22.005

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摘要目的建立高效液相色谱-三重四极杆/线性离子阱质谱法,同时测定大鼠血浆中4种广金钱草总黄酮活性成分(夏佛塔苷、维采宁-1、维采宁-2和维采宁-3)的方法,并应用此方法研究SD大鼠口服不同剂量广金钱草总黄酮后的体内药动学特征。方法液相色谱采用ACQUITY UPLC HSS T3柱(2.1 mm×50 mm,1.8 μm,Waters,USA),流动相为甲醇-水(含0.1%甲酸),梯度洗脱,质谱检测采用电喷雾(ESI-)离子源,多反应监测离子扫描模式(MRM)。结果大鼠血浆中4种黄酮成分在0.5～200.0 ng·mL^-1内呈良好线性关系,批内和批间精密度与准确度偏差均小于15%,回收率高且无基质效应,样品在处理、储存和分析过程中稳定性良好,可满足实验要求。大鼠口服不同剂量广金钱草总黄酮后各组分吸收较快,其中夏佛塔苷的血药浓度最高,之后依次是维采宁-3、维采宁-2和维采宁-1,各组分的体内暴露量和剂量呈正相关。结论本研究可为广金钱草总黄酮后续的人体药动学研究提供可靠的方法学参考和数据支持。

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	李雪
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	许羚
	郑培永
	杨铭

关键词 ：高效液相色谱-三重四极杆/线性离子阱质谱法, 广金钱草总黄酮, 药动学, 夏佛塔苷, 维采宁-1, 维采宁-2, 维采宁-3

Abstract：OBJECTIVE To develop a simple, sensitive and reliable method for simultaneous quantification of 4 biological active components of total flavonoids of Desmodium styracifolium (TFDS), including schaftoside, vicenin-1, vicenin-2 and vicenin-3, in the plasma of SD rats by HPLC-QTRAP-MS/MS, and study the pharmacokinetic characteristics of TFDS after oral administration of different doses (50, 100, 200 mg·kg^-1) in SD rats. METHODS The analytes were separated using an ACQUITY UPLC HSS T3 column with gradient elution, using mobile phase of methanol / water containing 0.1% formic acid (V/V). The detection was performed in negative multiple reaction monitoring (MRM) mode with electrospray ionization (ESI) source. RESULTS The calibration curves obtained were linear over the range from 0.5 to 200 ng·mL^-1. The relative standard deviations of intra-and inter-batch precision and assay accuracy were below 15.0% with high recovery. The analytes were proved to be stable during all sample storage, preparation and analytic procedures. The results of the pharmacokinetic studies of TFDS in SD rats showed the absorption of each component was fast. Among them, the plasma concentration of schaftoside was the highest, followed by vicenin-3, vicenin-2 and vicenin-1. A positive correlation has been observed between the C_max and AUC_0-t of active components and the dose of TFDS. CONCLUSION These studies could provide reliable reference data and theoretical support for the future clinical studies of TFDS.

Key words： HPLC-QTRAP-MS/MS total flavonoids of Desmodium styracifolium pharmacokinetic studie schaftoside vicenin-1 vicenin-2 vicenin-3

收稿日期: 2021-02-02

PACS:

R969.1

基金资助:国家自然科学基金青年基金项目资助( 81803825);国家十三五重大新药创制科技重大专项资助(2017ZX09304001);龙华医院第二批科研人才培养计划项目资助(RC-2020-02-04);第四批“龙医学者”育苗计划项目资助(YM2021016)

通讯作者: *杨铭,男,主任药师,硕士生导师研究方向:临床药理 Tel:(021)64289981

作者简介: 李雪,女,博士研究生,助理研究员研究方向:中药代谢和药代研究

引用本文:

李雪, 陈倩倩, 陈潮, 张天娇, 许羚, 郑培永, 杨铭. 高效液相色谱-三重四极杆/线性离子阱质谱法研究大鼠口服不同剂量广金钱草总黄酮后的药动学特征[J]. 中国药学杂志, 2021, 56(22): 1810-1817. LI Xue, CHEN Qian-qian, CHEN Chao, ZHANG Tian-jiao, XU Ling, ZHENG Pei-yong, YANG Ming. Pharmacokinetic Studies of Total Flavonoids of Desmodium Styracifolium After Oral Administration of Different Doses in SD Rats by HPLC-QTRAP-MS/MS. Chinese Pharmaceutical Journal, 2021, 56(22): 1810-1817.

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