高效液相色谱-质谱法测定人血浆中甘草次酸浓度及人体药代动力学研究

山东大学学报(医学版)

高效液相色谱-质谱法测定人血浆中甘草次酸浓度及人体药代动力学研究

赵文静，王本杰，魏春敏，袁桂艳，卜凡龙，郭瑞臣

山东大学齐鲁医院临床药理研究所，济南 250012

收稿日期:2008-03-05 修回日期:1900-01-01 出版日期:2008-11-16 发布日期:2008-11-16
通讯作者: 郭瑞臣

HPLC-MS determination and pharmacokinetic study of glycyrrhetic acid in human plasma

ZHAO Wen-jing, WANG Ben-jie, WEI Chun-min, YUAN Gui-yan, BU Fan-long, GUO Rui-chen

Institute of Clinical Pharmacology, Qilu Hospital of Shandong University， Jinan 250012， China

Received:2008-03-05 Revised:1900-01-01 Online:2008-11-16 Published:2008-11-16
Contact: GUO Rui-chen

摘要/Abstract

摘要： 目的建立人血浆中甘草次酸的高效液相色谱-质谱(LC-MS)测定法，并用于健康志愿者的药代动力学研究。方法20例健康志愿者一次口服甘草酸二铵胶囊150mg，采集肘静脉血并分离血浆，血样经乙酸乙酯提取后，以熊果酸为内标，进行LC-MS分析。色谱柱：Venusil XBP-C18柱(5μm, ID4.6×150mm)，流动相：甲醇(5mmol/L乙酸铵)-水(85∶15，V/V)，梯度洗脱；流速：0.8mL/min，柱温25℃，进样10μL。甘草次酸和内标熊果酸的检测离子和裂解电压分别为m/z 469.5、m/z 455.6和200V、100V。根据不同时间甘草次酸血浓度计算其药代动力学参数。结果在0.5～200ng/mL范围内，甘草次酸与内标的峰面积比值与浓度线性关系良好，相关系数为0.9974，定量限为0.5ng/mL，提取回收率为76.0%～80.0%,日内、日间RSD均小于12%。甘草次酸口服给药Cmax为(95.57±43.06)ng/mL，Tmax为(10.95±1.32)h。结论高效液相色谱-质谱测定法灵敏、准确、简便，适用于血浆甘草次酸的浓度测定及其人体药代动力学研究。

关键词: 高效液相色谱-质谱联用法, 药代动力学, 甘草次酸, 甘草酸二铵

Abstract: To develop a LC-MS method for the determination of glycyrrhetic acid in human plasma and for evaluation of its pharmacokinetic characteristics．Methods Glycyrrhetic acid in plasma was extracted with ethyl acetate， separated on a C18 column with a mobile phase of methanol(5mmol/L ammonium acetate)water(85∶15，V/V) and analyzed by the LCMS method with ursolic acid(UA) as the internal standard．The target ions were m/z 469.5 for glycyrrhetic acid and m/z 455.6 for internal standard. The fragmentor voltages were 200V for glycyrrhetic acid and 100V for the internal standard. ResultsThe calibration curve was linear over the range of 0.5 to 200ng/mL (r=0.9974). The quantitative limit for glycyrrhetic acid in plasma was 0.5ng/mL, the recovery rate was 76.0% to 80.0%, and the interday and intraday derivations (RSD) were less than 12%. The Cmax and Tmax of glycyrrhetic acid were (95.57±43.06)ng/mL and (10.95±1.32)h after oral administration. Conclusion The assay proved to be sensitive，accurate and convenient and can be applied in the determination of glycyrrhetic acid in human plasma and its pharmacokinetic study．

Key words: Diammoniu glycyrrhizinate, Glycyrrhetic acid, High performance liquid chromatographymass spectrometry, Pharmacokinetics

中图分类号:

R927.2

赵文静,王本杰,魏春敏,袁桂艳,卜凡龙,郭瑞臣. 高效液相色谱-质谱法测定人血浆中甘草次酸浓度及人体药代动力学研究[J]. 山东大学学报(医学版), 2008, 46(11): 1110-1112.

ZHAO Wen-jing,WANG Ben-jie,WEI Chun-min,YUAN Gui-yan,BU Fan-long,GUO Rui-chen. HPLC-MS determination and pharmacokinetic study of glycyrrhetic acid in human plasma[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(11): 1110-1112.

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