【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)100mg后,血样经乙酸乙酯提取后,进行LC-MS分析,色谱柱为LichrospherODS(5μm,100mm×4.6mm),流动相为乙腈-10mmol·L-1醋酸铵水溶液(90∶10),内标为熊果酸,检测离子为m/z469.5(甘草次酸)、m/z455.5(内标),裂解电压为200V。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。更多还原

【Abstract】 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 C_ 18 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 C_ max of glycyrrhetic acid in plasma was (65 ± 26) μg·L -1, the t_ max was (11.5 ± 2.3) h, the t_ 1/2 was (8.0 ± 2.2) h and the AUC_ 0-48 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.更多还原