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目的建立快速测定人血浆中磷酸苯丙哌林浓度的方法 ,并用于评价磷酸苯丙哌林缓释制剂的生物等效性。方法 24名健康志愿者分别单剂量空腹口服40mg磷酸苯丙哌林缓释片和缓释胶囊,给药后于不同时间收集血浆样品,采用液液萃取的方法进行生物样品前处理,采用LC-MS/MS法测定磷酸苯丙哌林在血浆中的浓度。用DASver2.1.1药动学软件进行数据处理并进行等效性分析。结果磷酸苯丙哌林浓度的线性范围为0.25～500ng·mL-1(r=0.9997),最低定量限为0.25ng·mL-1,最低定量限的RSD=8.78%;磷酸苯丙哌林及内标的萃取回收率均大于75%。日内、日间RSD均小于11%,高、中、低浓度血浆样品的平均方法回收率分别为100.41%、100.81%、105.96%。磷酸苯丙哌林缓释胶囊和缓释片的药动学参数:Tmax为4.21±0.55、4.19±0.51h;Cmax为82.12±14.27、78.43±10.44ng·mL-1;AUC0-72为2113.45±770.19、2076.89±818.25μg·h·L-1。结论所建方法灵敏、准确、专属性强,适用于磷酸苯丙哌林血药浓度的测定及其药动学的研究;受试制剂与参比制剂具有生物等效性。
Objective To establish a rapid method for the determination of concentration of benproperine phosphate in human plasma and to evaluate the bioequivalence of benproperine phosphate sustained-release preparation. Methods Twenty-four healthy volunteers were orally administered with 40 mg sustained-release tablets of benproperine phosphate and fast-release capsules respectively. The plasma samples were collected at different times after administration. The samples were pretreated with liquid-liquid extraction and analyzed by LC- Determination of Benproperine Phosphate in Human Plasma by MS / MS Method. DASver2.1.1 pharmacokinetic software for data processing and analysis of the equivalence. Results The linear range of benproperine phosphate concentration was 0.25-500 ng · mL-1 (r = 0.9997), the lowest limit of quantification was 0.25 ng · mL-1 and the lowest limit of quantification was 8.78%. Benproperine phosphate and Internal standard extraction recovery were greater than 75%. The intra-day and inter-day RSD were less than 11%. The average recovery rates of high, medium and low concentration plasma samples were 100.41%, 100.81% and 105.96%, respectively. Pharmacokinetic parameters of benproperine phosphate sustained release capsules and sustained release tablets: Tmax was 4.21 ± 0.55, 4.19 ± 0.51h; Cmax was 82.12 ± 14.27,78.43 ± 10.44ng · mL-1; AUC0-72 was 2113.45 ± 770.19, 2076.89 ± 818.25 μg · h · L -1. Conclusion The proposed method is sensitive, accurate and specific. It is suitable for the determination of the concentration of benproperine phosphate and its pharmacokinetics. The bioequivalence of the tested and reference preparations is validated.