超高效液相色谱-质谱联用技术分析中波紫外线辐射致抑郁模型大鼠口服 20(<i>S</i>)-人参皂苷Rg3的药代动力学行为

引用本文: 王恩鹏, 杜连云, 朱爽, 韩燕燕, 刘淑莹, 陈长宝, 李平亚. 超高效液相色谱-质谱联用技术分析中波紫外线辐射致抑郁模型大鼠口服 20(S)-人参皂苷Rg3的药代动力学行为[J]. 分析化学, 2021, 49(4): 618-627. doi: 10.19756/j.issn.0253-3820.211002 shu

Citation: WANG En-Peng, DU Lian-Yun, ZHU Shuang, HAN Yan-Yan, LIU Shu-Ying, CHEN Chang-Bao, LI Ping-Ya. Investigation of Pharmacokinetic Behavior of Depression Rats Caused by UVB Radiation after Oral Administration of 20(S)-Ginsenoside Rg3 by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry[J]. Chinese Journal of Analytical Chemistry, 2021, 49(4): 618-627. doi: 10.19756/j.issn.0253-3820.211002 shu

超高效液相色谱-质谱联用技术分析中波紫外线辐射致抑郁模型大鼠口服 20(S)-人参皂苷Rg3的药代动力学行为

王恩鹏 ^1,2, ,
杜连云 ^2, ,
朱爽 ^2, ,
韩燕燕 ^2, ,
刘淑莹 ^2, ,
陈长宝 ^{2,
,} ,
李平亚 ^{1,
,}

1.
吉林大学药学院, 长春 130021;
2.
长春中医药大学吉林省人参科学研究院, 长春 130117

通讯作者: 陈长宝,E-mail:ccb2021@126.com; 李平亚,E-mail:lipy@jlu.edu.cn

基金项目:
吉林省科技厅项目（No.20200404042YY）、国家重点研发计划项目（No.2019YFC1710704）和珈伊生化研发中心（苏州工业园区）有限公司资助。

摘要: 建立了以超高效液相色谱-三重四极杆质谱（UHPLC-QQQ-MS）同时检测大鼠血浆中20（S）-人参皂苷Rg3（20（S）-ginsenoside Rg3，G-Rg3）及其主要代谢产物20（S）-人参皂苷Rh2（20（S）-ginsenoside Rh2，G-Rh2）含量的快速分析方法，用于分析中波紫外线（UVB）辐射致抑郁模型大鼠口服G-Rg3后的药代动力学行为。选择Ascentis^® Express C₁₈色谱柱（5 mm×3 mm，2.7 μm），以0.1%甲酸-乙腈为流动相，梯度洗脱，流速为0.3 mL/min，进样量为5 μL，电喷雾离子源（ESI）在负离子模式下，对G-Rg3和G-Rh2进行定性与定量分析。定量分析选择多反应监测（MRM）模式进行扫描，以人参皂苷Rb1（20（S）-ginsenoside Rb1，G-Rb1）为内标（Internal standard，IS），离子对分别为m/z 783.5/621.4、621.4/459.4和1107.6/954.5。本方法的精密度、日内及日间准确率均满足药代动力学分析要求，10 min内即可完成全部分析。G-Rg3与G-Rh2分别在2.0~2500 ng/mL和2.0~2500 ng/mL范围内线性关系良好（R²>0.9907），G-Rg3经灌胃给药后在两组大鼠体内代谢过程皆符合二室模型特征，正常组和模型组t_1/2α分别为（0.35±0.116）h和（1.954±0.609）h，t_1/2β分别为（66.103±6.425）h和（52.496±33.639）h，AUC_（0-t）分别为（346.75±14.11）μg/（L·h）和（551.374±117.557）μg/（L·h），AUC_（0-∞）分别为（497.66±39.672）g/（L·h）和（694.523±213.077）g/（L·h）。两组之间的药代动力学参数具有显著差异（p<0.01），推断UVB辐射导致的抑郁作用可改变大鼠的机体内环境，影响G-Rg3的吸收与代谢。本方法简便、快速、选择性好、灵敏度高，适用于UVB辐射致抑郁模型大鼠的G-Rg3及其代谢产物G-Rh2的药代动力学研究。

关键词:

English

Investigation of Pharmacokinetic Behavior of Depression Rats Caused by UVB Radiation after Oral Administration of 20(S)-Ginsenoside Rg3 by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry

1.
School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China;
2.
Jilin Ginseng Academy, Changchun University of Traditional Chinese Medicine, Changchun 130117, China

Corresponding author: CHEN Chang-Bao, ; LI Ping-Ya,

Received Date: 02 January 2021
Revised Date: 31 January 2021
Fund Project:
Supported by the Jilin Province Science and Technology Development Project(No.20200404042YY), the National key Research and Development Projects (No.2019YFC1710704) and the Jiayi Biochemical Research and Development Center (Suzhou Industrial Park) Co., Ltd.

Abstract: A novel approach was developed for simultaneous determination of 20(S)-ginsenoside Rg3 (G-Rg3) and its main metabolite 20(S)-ginsenoside Rh2 (G-Rh2) in rats plasma by UHPLC-QQQ MS to compare the pharmacokinetic behavior of normal and UVB-induced depression model after oral administration of G-Rg3. In this method, an Ascentis^® Express C₁₈ chromatographic column (5 mm×3.0 mm, 2.7 μm) was used for qualitative and quantitative analysis of G-Rg3 and G-Rh2 under gradient elution with 0.1% formic acid in water-acetonitrile as the mobile phase. Simultaneously, the flow rate was 0.3 mL/min and the injection volume of sample solution was 5 μL. The MS analysis was operated in multiple-reaction monitoring (MRM) mode using electrospray ionization (ESI) under negative ion mode. With 20(S)-ginsenoside Rb1 (G-Rb1) as internal standard, G-Rg3 and G-Rh2 were quantitatively analyzed. The ions for quantification were m/z 783.5/621.4, 621.4/459 and 1107.6/954.5, respectively. The results showed that the intra-day and inter-day precisions, recovery, matrix effect and stability could meet the pharmacokinetic analysis requirement, and the whole analysis procedure could be completed in 10 minutes. Both G-Rg3 and G-Rh2 had a good linear relationship in the concentration ranges of 2.0-2500 ng/mL and 2.0-2500 ng/mL (R²>0.9907). The results indicated that the metabolic process of G-Rg3 conformed to a two-compartment pharmacokinetic model after single oral administration in the normal and model groups. The t_1/2α were (0.35±0.116) and (1.954±0.609) h, the t_1/2β were (66.103±6.425) and (52.496±33.639) h, the AUC_(0-t) were (346.75±14.108) and (551.374±117.557) mg·L/h, and the AUC_(0-t) were (497.66±39.673) and (694.523±213.077) mg·L/h. There were significant differences in pharmacokinetic parameters between the two groups (p<0.01), which was concluded that the internal environment of depression model rats might have been changed by UVB radiation, might also affecting the absorption and metabolism of G-Rg3. This method was simple, rapid, selective and sensitive, and could be used for the pharmacokinetic analysis of Rg3 and Rh2. More important, it was suitable for pharmacokinetic study of G-Rg3 in vivo.

Key words:

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

超高效液相色谱-质谱联用技术分析中波紫外线辐射致抑郁模型大鼠口服 20(S)-人参皂苷Rg3的药代动力学行为

通讯作者: 陈长宝,E-mail:ccb2021@126.com; 李平亚,E-mail:lipy@jlu.edu.cn

English

Investigation of Pharmacokinetic Behavior of Depression Rats Caused by UVB Radiation after Oral Administration of 20(S)-Ginsenoside Rg3 by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry

Corresponding author: CHEN Chang-Bao, ; LI Ping-Ya,

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

超高效液相色谱-质谱联用技术分析 中波紫外线辐射致抑郁模型大鼠口服 20(S)-人参皂苷Rg3的药代动力学行为

通讯作者: 陈长宝,E-mail:ccb2021@126.com; 李平亚,E-mail:lipy@jlu.edu.cn

English

Investigation of Pharmacokinetic Behavior of Depression Rats Caused by UVB Radiation after Oral Administration of 20(S)-Ginsenoside Rg3 by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry

Corresponding author: CHEN Chang-Bao, ; LI Ping-Ya,

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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