HPLC测定人血浆中茴三硫代谢产物对羟基茴三硫及相对生物利用度  

HPLC determination of 4-hydroxy-anetholtrithion in human plasma and study on the bioequivalence of anetholtrithion tablets

作　　者：贺凌云[1] 曹亚杰[1] 胡晓蕾[1] 李筱旻[1] 王黎青[1] 郭歆[1] 程泽能[1] 

机构地区：[1]中南大学药学院药物分析教研室,长沙410013

出　　处：《药物分析杂志》2007年第4期545-547,共3页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立了人血浆中茴三硫代谢产物对羟基茴三硫的HPLC测定法,研究2种茴三硫片在正常人中的相对生物利用度。方法:以吴茱萸次碱为内标,血样采用乙酸乙酯(5%异丙醇)1次提取,经Diamonsil C_(18)柱分离后在355nm波长处测定。20名健康志愿者采用自身对照随机交叉试验设计,分别单剂量口服茴三硫75mg后测定两者相对生物利用度。结果:对羟基茴三硫与内标分离度好,内源性杂质不干扰测定,对羟基茴三硫的线性范围为15.6～2000ng·mL^(-1),最低检测限为10ng·mL^(-1),提取回收率在80%以上;日内、日间精密度的相对标准偏差均小于10%。单次服用75mg茴三硫片试验制剂或参比制剂后的药代动力学参数AUC(0→12)分别为(971.8±368.0)ng·h·mL^(-1)和(1004.6±391.7)ng·h·mL^(-1),C_(max)分别为(323.3±209.4)ng·mL^(-1)和(279.5±107.0)ng·mL^(-1),T_(max)分别为(1.5±0.3)h和(1.6±0.4)h。相对生物利用度为97.3±6.8%。结论:该方法快速,简便,灵敏,重复性好,可用于对羟基茴三硫在人体内过程研究。方差分析结果表明2种制剂的主要药代动力学参数之间无明显差异,双单侧t检验结果表明两种制剂为生物等效制剂。Objective：A method for determining metabolite of anethohrithion in human plasma by high performance liquid chromatography was developed. Method ：4 - hydroxy - anethotrithion, the main active metabolite of anethohrithion was successfully separated using a Diamonsil CIS column and determinated at 355 nm. The internal standard was rutaecarpine,the plasma samples were extracted by ethyl acetate （5% isopropanol）. A single oral dose of 75 mg anethohrithion tablets was administered to 20 healthy volunteers in a randomized crossover study. 4 - hydroxy - anethotrithion concentration in plasma was determined by HPLC, and the pharmacokinetics and bioavailability were studied. Results：The linear range of 4 - hydroxy - anothohrithion was 15.6 - 2000 ng · mL^-1, the detection limit was 10 ng · mL^-1. The extraction recovery was more than 80% ; Intra - day RSD and inter - day were less than 10%.The AUC0→12 of the tow tablets were （971.8 ±368.0） ng · h ·mL^-1 and （1004.6±391.7） ng h ·mL^-1,Cmax were （323.3 ±209.4） ng ·mL^-1 and （279.5 ±107.0） ng ·mL^-1,Tmax were （1.5 ±0.3）h and （1.6 ± 0.4） h, respectively, the relative bioavailability of the test preparation was 97.3 ± 6. 8 %. Conclusion： Results of statistics show there were no significant differences between the two preparations, and bioequivalence is observed. The established HPLC method is accuracy and sensible for 4 - hydroxy - anethotrithion determination.

关 键 词：茴三硫 对羟基茴三硫 HPLC 血浆 相对生物利用度 

分 类 号：R917[医药卫生—药物分析学]