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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 dissociate the hydroxyphenyltrithione from the metabolites of anisodithiolane by enzymolysis method and establish HPLC method to determine its content. To study the pharmacokinetics of hydroxyphenyltrithione in human body , And evaluated the bioequivalence of anetholing tablets. Methods: Glucose was depolymerized by β-glucuronidase to make the plasma anisotetrathiolate metabolites free of hydroxyphenyltrithione. HPLC-UV method was used to determine the plasma concentration. Stationary phase: C18 column, mobile Phase: methanol-water (80:20, v / v), flow rate: 1.0 mL · min -1, column temperature: 30 ° C, detection wavelength: 346 nm, injection volume: 20 μL. DAS2.0 software was used to process blood concentration data and calculate parameters, and statistical analysis. Results: The HPLC method was established for the determination of p-hydroxyphenyltrithione in plasma. The linear range was 20-1500 ng · mL-1, r = 0.9992, and the lowest detection limit was 10 ng · mL-1. The extraction recovery The recoveries ranged from 32.2% to 44.0%. The method recoveries ranged from 102.5% to 107.0%. The intra-day and inter-day RSDs were all less than 9%. Conclusion: The method used in this study has high sensitivity, specificity and repeatability to the determination of hydroxyphenyltrithione plasma concentration, and the results are reliable. Statistical analysis shows that there are no significant pharmacokinetic parameters of the two preparations Differences, with bioequivalence.