HPLC-荧光检测法测定犬血中紫花前胡苷的浓度及其药代动力学初步研究  

Determination of nodakenin in Beagle dog's plasma by HPLC and its pharmacokinetics

作　　者：李婧[1] 孙文霞 

机构地区：[1]西南民族大学化学与环境保护工程学院,成都610041 [2]四川抗菌素研究所有限公司,成都610051

出　　处：《药物分析杂志》2013年第3期367-370,共4页Chinese Journal of Pharmaceutical Analysis

基　　金：西南民族大学2011中央高校基本科研业务费专项资金项目(No:11NZYTD06)

摘　　要：目的:建立HPLC-荧光法测定犬血浆中紫花前胡苷的浓度,初步研究紫花前胡苷在犬体内的药代动力学特征。方法:以乙腈为蛋白沉淀剂,以Hypersil BDS C18柱(200 mm#4.6 mm,5μm)为色谱柱,流动相为甲醇-0.1%磷酸溶液(45∶55);激发波长为360 nm;发射波长为395 nm。Beagle犬4只,单次静脉注射紫花前胡苷30 mg·kg-1,后肢静脉取血,采用HPLC测定血药浓度,并用DAS 2.0程序计算药代学参数。结果:Beagle犬血浆中内源性成分对测定无干扰,紫花前胡苷的线性范围为0.1～40.0μg·mL-1(r=0.9993),平均相对回收率为89.8%～100.7%,日内和日间RSD均<10%。紫花前胡苷在犬体内的药代动力学过程符合开放二房室模型,主要药代动力学参数t1/2α、t1/2β、V1、CL和AUC(0-t)分别为(0.536±0.085)h、(3.048±0.826)h、(0.446±0.038)L·kg-1、(0.417±0.108)L·h-1.kg-1和(68.966±16.181)mg·L-1.h。结论:本方法准确、灵敏、快速,适用于紫花前胡苷的血药浓度测定和药代动力学研究,为紫花前胡苷的开发和临床应用提供参考。Objective：To establish a sensitive and reliable HPLC -fluorescence method to determine the concentra- tion of nodakenin in Beagle dogs＇ plasma, and to investigate its pharmacokinetics. Methods： The plasma samples were pretreated by acetonitrile for protein precipitation and were analyzed by HPLC. Separation and determination were achieved on a Hypersil BDS column （ 200 mm × 4.6 mm, 5 μm） with the mobile phase consisting of 0.1% phosphoric acid - methanol （55：45 ）. The excitation wavelength and the emission wavelength were set at 360 nm and 395 nm, respectively. Four dogs were administered with nodakenln by intravenous injection at a single dose of 30 mg · kg- 1. The blood for test was taken from the vein on the posterior limb, and the plasma concentration was determined by HPLC. The main parameters of pharmacokineties were calculated by DAS 2.0 software. Results ： The endogenous ingredients in the Beagle dog blood showed no interference to the determination. The range of linearity was 0.1 -40.0 μg · mL-1 （r =0. 9993）. And the mean recovery rate was 89.8% - 100.7%. Both the intra - day and inter - day RSDs were less than 10%. The plasma concentration - time curve of nodakenin was conformed to be a two - compartment open model. The main pharmacokinetic parameters t1/2α, t1/2β, V1 , CL and AUC（0-t） were （0.536 ±0.085）h,（3.048 ±0.826）h,（0.446 ±0.038）L · kg-1,（0.417±0. 108） L · h-1 · kg-1 and（68.966 ±16.181 ） mg· L - 1 . h, respectively. Conclusion： This method is accurate, sensitive, rapid, and suitable for plas- ma concentration determination and pharmacokinetic research of nodakenin, providing reference for its developmentand application.

关 键 词：紫花前胡苷 高效液相色谱法 荧光法检测法 比格犬 血浆样品 药代动力学 

分 类 号：R917[医药卫生—药物分析学]