石丹颗粒的药动学研究

Pharmacokinetic Study of Shi Dan Granules

目的考察石丹颗粒中的指标性成分在大鼠体内的药动学特征,建立LC-MS/MS法同时测定大鼠血浆中毛蕊异黄酮葡萄糖苷、迷迭香酸、甘草苷的血药浓度。方法以淫羊藿苷为内标,血浆样品乙腈沉淀后,经LC-MS/MS分离分析,采用Agilent ZORBAX SB-C18色谱柱(250mm×4.6mm,5μm);流动相为A乙腈,B:0.1%的甲酸水溶液,梯度洗脱:0~10min,A-B(12∶88)~A-B(68∶32);10~11min,A-B(68∶32)~A-B(12∶88);11~15min,A-B(12∶88)~A-B(12∶88);流速:1m L·min-1;采用电喷雾离子源(ESI);以离子监测(SIR)扫描方式对正负离子进行监测。结果根据药动学参数得到,毛蕊异黄酮葡萄糖苷达峰时间为32.5min,迷迭香酸的达峰时间在25min,甘草苷的达峰时间为32.5min。3种成分的半衰期分别为:140min、98min、762min。结论该方法准确、灵敏、稳定性好、回收率高,适用于石丹颗粒药动学的研究。

OBJECTIVE To investigate pharmacokinetic characteristics of composition index of Shi Dan gran- ules in rat,to establish a high performance liquid chromatography tandem mass spectrometry （LC-MS/MS） method for the determination of blood drug concentration of calycosin-7-O-β-D-lucopyranoside, rosemary acid and liquiritin in rat plasma, and apply to its clinical pharmacokinetics. METHODS Plasma samples were precipitated with acetoni- trile and determined by LC-MS/MS using epimedium glycoside as an internal standard. The separation was carried out on a Diamonsil ClS column （ 250mm × 4. 6mm, 5 μm） with a mobile phase of A cetonitrile, B water （ containing 0. 1% formic acid） ,and with gradient elution,0 - 10min,A-B（12：88） - A-B（68：32） ; 10 -11min,A-B（68： 32） A-B （ 12：88 ） ; 11 - 15min, A-B （ 12：88 ） - A-B （ 12：88 ）, with a flow rate lmL ·min -1. ESI was performed in the SIR, positive and negative ions was monitored by ionmonitoring. RESULTS according to the pharmacokinetic pa- rameters, calycosin separately glycosidase tmax was 32. 5min, rosemary acid tmax in 25min, licorice glycosides tmax was 32. 5min. The half-life of three components：140min ,98min,98min. CONCLUSION This method was sensitiv- ity and precision and is suitable for plasma concentration monitoring and pharmacokinetic studies of Shi Dan gran- ules.