液相色谱-质谱联用法测定人血浆中法莫替丁胶囊含量及其生物等效性评价

发布时间：2018-02-20 21:08

  本文关键词： 法莫替丁 LC/MS/MS 人血浆 生物等效性　出处：《复旦学报(医学版)》2015年04期 　论文类型：期刊论文

【摘要】：目的建立快速灵敏的液相色谱-质谱联用(LC/MS/MS)法测定人血浆中法莫替丁的含量,并比较两种法莫替丁胶囊在健康人体内的药动学及生物等效性。方法血浆样品中的蛋白经甲醇白沉淀处理后,采用LC/MS/MS系统分析,色谱柱为Venusil XBP苯基桩(100 mm×2.1 mm,5μm),以0.1%甲酸水溶液-甲醇(体积分数为60∶40)为流动相,通过电喷雾离子化四级杆串联质谱,以多反应监测(multiple-reaction monitoring,MRM)方式进行检测;采用DAS 2.1.1软件进行药动学参数的数据处理。结果此法在标准曲线范围2.5~250.0ng/mL(r=0.999 9)内线性良好,最低定量限为2.5 ng/mL;定量限、低、中、高浓度的方法回收率为97.23%~99.64%,批内和批间精密度RSD值为2.30%~4.32%,且提取回收率稳定并均大于80%;基质效应为89.01%~95.73%。两种胶囊的血药浓度-时间曲线基本一致,主要药动学参数cmax、AUC0-t、AUC0-∞差异均无统计学意义,tmax经非参数法检验差异无统计学意义。结论采用此方法测定血浆药物浓度时,灵敏度高、准确度和精密度好,样品处理简单,分析测试速度快;试验胶囊的相对生物利用度为91.5%±24.5%(n=23,AUC0~t)或90.7%±24.5%(n=23,AUC0~∞),统计分析表明两种胶囊生物等效。
[Abstract]:Objective to establish a rapid and sensitive liquid chromatography-mass spectrometry (LC-MS) method for the determination of famotidine in human plasma. The pharmacokinetics and bioequivalence of two kinds of famotidine capsules in healthy volunteers were compared. Methods the proteins in plasma samples were treated by methanol white precipitation and analyzed by LC/MS/MS system. The chromatographic column was Venusil XBP phenyl piling (100mm 脳 2.1mm ~ 5 渭 m). The mobile phase consisted of 0.1% formic acid aqueous solution and methanol (60: 40) as mobile phase. The method of electrospray ionization four-pole tandem mass spectrometry was used to monitor multiple-reaction monitoring. DAS 2.1.1 software was used to process the data of pharmacokinetic parameters. Results this method has good linearity in the standard curve range of 2.5 ~ 250.0ng / mLL ~ (0.999 ~ 9). The lowest quantitative limit is 2.5 ng / mL; The recovery rate of high concentration was 97.23 ~ 99.64, the RSD value of intra- and inter-assay precision was 2.30 and 4.322.The recovery was stable and greater than 80, the matrix effect was 89.01 and 95.73.The plasma concentration-time curves of the two capsules were basically the same. There was no significant difference in the main pharmacokinetic parameters (cmaxAX AUC0-tAUC 0- 鈭，

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