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目的:建立同时测定人血浆中氯雷他定和硫酸伪麻黄碱血药浓度的LC-MS定量方法,考察健康志愿者服用国产复方氯雷他定缓释胶囊后氯雷他定和硫酸伪麻黄碱的药动学参数。方法:血浆样品经碱化和液-液萃取后,以乙腈-0·02%醋酸铵为流动相,经Hypersil-ODS柱分离,采用离子源为ESI源的LC-MS测定样品,临床试验方案采用双交叉试验设计法。测定志愿者单剂量以及多剂量口服复方氯雷他定缓释胶囊后的血药浓度,并对供试制剂与参比制剂的生物等效性进行评价。结果:血浆中样品线性关系较好(r=0·9999,r=0·9998),氯雷他定和硫酸伪麻黄碱的绝对回收率均大于70%,最低检测浓度分别为0·50和5·0ng·mL-1。应用本法测定20例志愿者单剂量及多剂量交叉口服供试制剂与参比制剂后的血药浓度经时过程,测得二者的主要药动学参数无显著性差异,二者生物等效。结论:本方法专属性强,灵敏度高,操作简便、快速,符合生物样品分析要求,适用于临床药动学研究。
OBJECTIVE: To establish a LC-MS quantitative method for the simultaneous determination of loratadine and pseudoephedrine sulfate in human plasma and study the pharmacokinetics of loratadine and pseudoephedrine sulfate in Chinese healthy volunteers after taking domestic loratadine capsules Learning parameters. Methods: The plasma samples were alkalinized and liquid-liquid extracted. The samples were separated on a Hypersil-ODS column using acetonitrile-0.02% ammonium acetate as mobile phase. Double crossover test design method. The plasma concentration of single dose of volunteers and multi-dose oral loratadine capsules were determined, and the bioequivalence of test preparations and reference preparations was evaluated. RESULTS: The linearity of the samples in plasma was better (r = 0.99999, r = 0.9998). The absolute recoveries of loratadine and pseudoephedrine sulfate were both above 70% with the lowest detection concentrations of 0 · 50 and 5 · 0 ng · mL-1. This method was used to determine the time course of plasma concentration of single and multiple doses of crossover oral administration of test preparations and reference preparations in 20 volunteers. There was no significant difference in the main pharmacokinetic parameters between the two groups. effect. Conclusion: The method is highly specific, sensitive, easy to operate, fast and meets the requirements of biological sample analysis, suitable for clinical pharmacokinetic studies.