RP-HPLC法测定血浆中栀子苷浓度及药动学研究

RP -HPLC Determination of Geniposide in Plasma and Study on Its Pharmacokinetics in Mice

目的:建立反相高效液相色谱法测定血浆中栀子苷的浓度,研究比较栀子药材及其制剂加味逍遥丸和清开灵注射液中栀子苷在小鼠体内的药动学行为。方法:血浆样品用甲醇沉淀蛋白后,采用Kromasil C18色谱柱(250 mm×4.6 mm,5μm),柱温:室温;流动相:乙腈-水(10:90);流速:1.0 mL·min-1;检测波长238 nm,进样量20μL。结果:线性范围1.02-51.0μg·mL-1(r=0.9992);最低检测浓度0.255μg·mL-1;回收率分别为93.14%,91.90%,108.2%;日内和日间精密度RSD均小于10%。小鼠灌胃栀子提取液和加味逍遥丸提取液后栀子苷的药动学行为均符合一室模型,而小鼠静脉注射栀子提取液和清开灵注射液后栀子苷的药动学行为均符合二室模型。结论:2种不同的提取液以相同途径给予栀子苷后,药材和制剂中栀子苷的房室模型没有改变,但灌胃加味逍遥丸比栀子药材的分布及消除半衰期长,达峰时间长,达峰浓度低;静注清开灵注射液比栀子药材的分布及消除半衰期短、消除速率快。

Objective: To establish a RP-HPLC method for determination of geniposide in Gardenia and the preparations including Jiawei Xiaoyao pills and Qingkailing injection containing Gardenia in mice plasma;To study and compare the pharmacokinetic characteristics of geniposide in mice. Methods: After the plasma protein was precipitated, geniposide was separated well on a Kromasil C18 column(250 mm×4. 6 mm,5μm)under room temperature. The mobile phase was a mixture of acetonitrile - water (10:90 ) at a flow rate of 1.0 mL·min-1. The UV detection was set at 238 nm. Results:The calibration curve was linear in the range of 1. 02-51. 0μg·mL-1 (r=0.9992). The lowest limit was 0.255μg·mL-1 and the recovery was 91. 90%-108. 2%. The RSD values of within - day and between - day precision were less than 10% . The concentration - time curves of geniposide after ig administration were both confirmed to one - compartment open models, and the concentration - time curves after iv administration were both confirmed to two - compartment open models. Conclusion:The results show the same compartment model for Gardenia and its preparations after same administration, but the geniposides pharamacokinetic parameters of Gardenia were not same as those of its preparations.