【摘要】 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。更多还原

【Abstract】 Objective:To assess pharmacokinetics of loratadine and pseudoephedrine in healthy volunteers, following after the establishment of a LC-MS method for the simultaneous determination of plasma loratadine and pseudoephedrine. Methods:A randomized and crossover doses clinical study recruited 20 healthy volunteers, who were orally administrated with a single dose or multiple doses of loratadine and pseudoephedrine. The plasma samples from the volunteers were obtained by alkalization and liquid-liquid extraction. A liquid chromatography-mass spectrum （LC-MS） equipped with electrospray ionization （ESI） source was used to assay the plasma samples. The LC-MS was conducted under a Hypersil-ODS column and the mobile eluent of CH₃CN-0.02%NH₄Ac （80∶20）. The bioavailability of loratadine and pseudoephedrine was determined by using the LC-MS.Results:The calibrated linear curve was in the range of 0.5～5.0 ng.mL -1 for loratadine and 5.0～ 1 000.0ng·mL -1 for pseudoephedrine （r= 0.999 9,r= 0.999 8） with the detection limit of 0.5 ng·mL -1 and 5.0 ng·mL -1, respectively. The test capsules of loratadine and pseudoephedrine were bioequivalent to the reference tablets of loratadine and pseudoephedrine.Conclusion:This specific, sensitive and reliable LC-MS method offers an alternative to monitor and evaluate the pharmacokinetics of loratadine and pseudoephedrine.更多还原