UPLC法测定大鼠血浆中Liguzinediol浓度以及动力学研究

Determination of Liguzinediol and its pharmacokinetics in rat by ultra performance of liquid chromatograph

目的建立测定大鼠血浆中Liguzinediol浓度的UPLC测定方法,探讨其在大鼠体内的药代动力学。方法血浆样品经甲醇提取后,上清液经N2吹干流动相复溶后注入UPLC分析,色谱柱为UPLC HSS T3柱(2.1 mm×100 mm,1.8μm),流动相为甲醇-水(28∶72,V∶V),流速为0.4 ml.min-1,检测波长278 nm。SD大鼠6只,iv给药10 mg.kg-1后,用UPLC法测定给药后大鼠血浆中Liguzinediol的浓度,利用DAS软件拟合并计算其药代动力学参数。结果 Ligu-zinediol的血药浓度在0.41～52.4 mg.L-1范围内呈线性,提取回收率均>80%,日内、日间精密度<10%,符合生物样品分析要求。大鼠静脉注射10 mg.kg-1的Liguzinediol,其血药浓度(C)-时间(t)曲线呈二室模型,主要药动学参数T12β、AUC(0-∞)、CL分别为1.62 h、18.36 mg.h.L-1、0.71 L.h-1.kg-1。结论该方法操作简便、快速、专属性强,可用于Liguzinediol的药代动力学及成药性研究。

Aim To establish a simple and accurate method for determination of Liguzinediol by ultra performance liquid chromatography（UPLC） and study the pharmacokinetics of Liguzinediol in rats.Methods Liguzinediol was extracted from plasma with methanol,and analyzed by UPLC with an Acquity UPLC HSS T3 column（2.1 mm×100 mm,1.8 μm） at 278 nm.Methanol and water（28 ∶ 72） were used as the mobile phase.The flow rate was 0.4 ml·min^-1.Six rats was given 10 mg·kg^-1 Liguzinediol via iv,drug plasma concentration was determined by UPLC and pharmacokinetic parameters were evaluated by DAS Software.Results Calibration curve was linear within the range of 0.41-52.4 mg·L^-1.The extract recoveries of Liguzinediol were more than 80%.RSD of inter-day and intra-day assay was limited in 10%.The concentration-time courses of liguzinediol were best fitted to a two compartment open model.The main pharmacokinetic parameters of T1 2β,AUC（0-∞）,CL were 1.62 h,18.36 mg·h·L^-1,0.71 L·h^-1·kg^-1 respectively.Conclusions The method is simple,rapid and accurate.It has a good reproducibility and stability,which may be used for plasma concentration monitoring and pharmacokinetics study for Liguzinediol.