高效液相色谱-质谱法研究甘草酸二铵胶囊在健康人体的药代动力学  

Study on the pharmacokinetics of diammonium glycyrrhizinate capsule in healthy volunteers by HPLC-MS

作　　者：黄鑫[1] 丁黎[1] 杨劲[1] 卞晓洁[1] 张陆勇[1] 张正行[1] 刘广余[2] 

机构地区：[1]中国药科大学,江苏南京210009 [2]南京医科大学第一附属医院国家药品临床研究基地,江苏南京210029

出　　处：《中国临床药理学杂志》2006年第5期365-368,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 建立人血浆中甘草次酸的高效液相色谱-质谱测定法,并研究其在健康志愿者的药代动力学.方法 口服甘草酸二铵胶囊（抗炎保肝药）100 mg后,血样经乙酸乙酯提取后,进行LC-MS分析,色谱柱为LichrospherODS（5 μm,100 mm×4.6 mm）,流动相为乙腈-10 mmol·L^-1醋酸铵水溶液（90：10）,内标为熊果酸,检测离子为m/z 469.5（甘草次酸）、m/z 455.5（内标）,裂解电压为200 V.测定甘草次酸的血药浓度,计算其药代动力学参数.结果 在0.1～400μg·L^-1内,甘草次酸与内标的峰面积比值与浓度的线性关系良好,定量限为0.1μg·L^-1,提取回收率为88.0%～98.0%.人体中甘草次酸药代动力学参数：Cmax为（65±26）μg·L^-1,tmax为（11.5±2.3）h,t1/2为（8.0±2.2）h,AUC0-48为（1006±426）μg·h·L^-1.结论 本方法灵敏、准确、简便,适于临床药代动力学研究.Objective To develop an LC -MS assay for determination of glycyrrhetic acid in human plasma and to estimate the pharmacokine - tics of glycyrrhetic acid in human. Methods After being extracted with ethyl acetate, plasma was separated using a C18 column with a mobile phase of 10 mmol · L^-1 ammonium acetate - acetonitril （ 10： 90） and analysied by MS detector, Ursolic acid was the internal standard. The target ions were m/z 469, 5 for glycyrrhetic acid and m/z 455, 5 for the internal standard, The fragmentor voltage was 200 V, A clinical trial was performed in 20 healthy volunteers, in which a single 100 mg dose of diammonium glycyrrhizinate was administered to each volunteer, Results Calibration curve was linear over the range of 0.1 -400 μg · L^-1, The limit of quantitation for glycyrrhetic acid in plasma was 0, 1 μg · L^ 1, The recovery was 88.0% - 98, 0%. The Cmax of glycyrrhetic acid in plasma was （65 ± 26） μg · L ^-1, the tmax was （ 11.5 ± 2. 3） h, the t1/2 was （8.0 ± 2.2） h and the AUC0-48 was （1006 ± 426） μg· h · L^-1. Conclusion The assay was proved to be sensitive accurate and convenient, It can be applied to the pharmacokinetic study of glycyrrhetic acid in human.

关 键 词：甘草酸二铵 甘草次酸 高效液相色谱-质谱 药代动力学 

分 类 号：R969.1[医药卫生—药理学] R976[医药卫生—药学]