酶解-HPLC法测定茴三硫代谢物及人体药代动力学研究  

Zymolysis-HPLC determination of the metabolite of anethol trithione and study on pharmacokinetics in human plasma

作　　者：邓俊刚[1] 李茜[2] 乔健[2] 

机构地区：[1]桂林医学院附属医院,桂林541001 [2]武汉生物制品研究所,武汉430022

出　　处：《药物分析杂志》2010年第12期2275-2278,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:用酶解法解离茴三硫体内代谢物对羟基苯基三硫酮,建立HPLC方法检测其含量,研究茴三硫体内代谢物对羟基苯基三硫酮在人体内的药代动力学,并评价茴三硫片剂的生物等效性。方法:用β-葡糖苷酸酶酶解脱去葡萄糖,使血浆中茴三硫代谢物对羟基苯基三硫酮游离后用HPLC-UV法测定其血浆中浓度;固定相:C18色谱柱,流动相:甲醇-水(80∶20,v/v),流速:1.0mL·min-1,柱温:30℃,检测波长:346nm,进样量:20μL。运用DAS2.0软件处理血药浓度数据和计算参数,并进行统计学分析。结果:建立的HPLC法测定血浆中对羟基苯基三硫酮浓度,专属性强,线性范围为20～1500ng·mL-1,r=0.9992,最低检测限为10ng·mL-1;提取回收率为32.2%～44.0%,方法回收率为102.5%～107.0%,日内、日间RSD均小于9%。结论:本项研究所用方法对羟基苯基三硫酮血药浓度检测灵敏度高、特异性强、重复性好,测定结果可靠,统计学分析表明2种制剂的主要药代动力学参数无显著性差异,具生物等效性。Objective：To establish HPLC method to detect the metabolite of anethol trithione（4-hydroxy-anethol trithione,ATX）in vivo after zymolysis and research the pharmacokinetics,evaluate the bioequivalence of two different anethol trithione tablets.Methods：The method entailed enzymatic hydrolysis of human plasma samples via β-glucuronidase,ATX concentration was determined by HPLC with a reverse phase C18 column,mobile phase consisted of a mixture of methanol-water（80∶20）was delivered at a flow rate of 1.0 mL·min-1.The injection volume was 20 μL and the detection was performed at a wavelength of 346 nm.The pharmacokinetics parameters and relative bioavailability were calculated on the basis of compartment models by using DAS 2.0 program to evaluate the bioequivalence of two preparations.Results：The method of HPLC was effectively in determining 4-hydroxy-anethole trithione ATX in human plasma.It was validated and proved to be linear in the range of 20-1500 ng·mL-1;and the limit of quantification concentration（LOQ）in plasma was 10 ng·mL-1.The estration recovery was 32.2%-44.0% and the method recovery was 102.5%-107.0%;.The intra-day and inter-day RSDs were less than 9%.Conclusion：The method of HPLC in determining ATX was sensitive,specific and simple,the result shows that the two tablets are bioequivalent.

关 键 词：茴三硫 对羟基苯基三硫酮 药代动力学 β-葡糖苷酸酶 高效液相色谱 

分 类 号：R917[医药卫生—药物分析学]