摘要
目的建立大鼠血浆中芍药苷的LC-MS/MS定量分析方法,并用于大鼠体内芍药苷的药物动力学研究。方法色谱柱为岛津ODS(250mm×2.0mm),流动相为甲醇-0.1%甲酸溶液(70∶30)。采用四级杆质谱仪进行选择反应检测(SRM),电喷雾离子源。生物样品预处理采用乙酸乙酯液-液萃取法。考察3个剂量芍药苷灌胃给药后,大鼠体内的药物动力学特征。结果通过该测定方法,芍药苷峰与内标峰可完全分离,生物样品中杂质不干扰样品测定,具有较高的专属性。血浆中芍药苷最低检测限为5μg/L,线性范围:5～5000μg/L;相对回收率>90%,绝对回收率>70%。日内和日间RSD均<15.0%,样品在室温放置、冷冻储存、反复冻融条件下基本稳定。灌胃给予芍药苷后,其血药浓度-时间过程符合W=1的二室模型特征,由药动学参数可知,按3个不同剂量(25、50、100mg/kg)分别灌胃给予大鼠芍药苷后,血浆中的芍药苷浓度在3.8h左右达峰,t1/2α分别为0.926、1.106、1.601h,t1/2β分别为1.96、1.654、2.001h。结论灌胃给予芍药苷后,芍药苷在大鼠体内吸收、消除较快,具有线性动力学特征。所建立方法可用于芍药苷的药物动力学研究。
Objective To develop a rapid, sensitive and selective liquid chromatography tandem spectrometry method for the determination of paeoniflorin in rat plasma,and to investigate its pharmacokinetics parameters in rats. Methods HPLC analysis was carried out on a C18 column（250 mm ×2.0 mm） with a mobile phase consisting of methanol and 0. 1% formic acid（70 ： 30）. Deteetion was carried out on a triple quadrupole tandem mass speetrom- eter by selected reaction monitoring and an electrospray ionization source. The phamacokinetic characteristics of paeoniflorin was investigated after oral adminstration to rats in three dosages. Pharmacokinetie parameters were calculated with DAS2.0 practical pharmacokinetics program. Results The linearity range for Pae in plasma in rats was obtained from 5 μg/L to 5 000μg/L. The recoveries was more than 90% （n = 5 ） ,The relative standard deviations of the intra-day and inter-day were less than 15% （n =5 ）. The mean plasma concentrations of Pae after ig Pae in rats（25,50,100 mg/kg） could be fitted to a two-compartment model with a weigh of 1. tmax was 3. 8 h. t1/2α were 0. 926,1. 106,1. 601 h, t1/2β were 1.96,1. 654,2. 001 h. Conclusion The method can be applied to study of pharmacokinetics of paeoniflorin. The results indieate that Pae is absorbed and eliminated rapidly. The pharmacokinetics of pae can be complied with linear kinetic course.
出处
《安徽医科大学学报》
CAS
北大核心
2009年第6期707-711,共5页
Acta Universitatis Medicinalis Anhui
