利伐沙班和瑞格列奈在大鼠体内药动学相互作用

发布时间：2018-03-18 23:36

  本文选题：高效液相色谱-串联质谱　切入点：利伐沙班　出处：《中国新药杂志》2017年06期 　论文类型：期刊论文

【摘要】：目的:建立高效液相色谱-串联质谱(HPLC-MS/MS)法,同时测定大鼠血浆中利伐沙班和瑞格列奈浓度,并初步考察两药的药动学相互作用。方法:将54只雄性wistar大鼠随机分为单用利伐沙班组、单用瑞格列奈组和联合用药组,每组18只,于给药前后不同时间点眼内眦采集血样,采用HPLC-MS/MS法同时测定两药的血药浓度。色谱柱为Diamonsil C18柱,流动相为乙腈-0.1%甲酸水溶液(60∶40),质谱条件为电喷雾离子源(ESI源),正离子模式检测,扫描方式为多反应监测(MRM),用于定量分析的离子反应分别为m/z 436.0→m/z144.9(利伐沙班)、m/z 452.9→m/z 162.3(瑞格列奈)和m/z 324.1→m/z 127.2(格列齐特)。利伐沙班、瑞格列奈检测质量浓度线性范围分别为12.5~800 ng·m L-1(r=0.997 1)和2.5~160 ng·m L-1(r=9 995)。结果:与单用瑞格列奈组相比,联合用药组瑞格列奈各项参数没有显著变化;与单用利伐沙班组相比,联合用药组利伐沙班AUC0-24,AUC0-∞和Cmax明显增大(P0.05),清除率(CL)明显减小(P0.05)。结论:该方法专属性强、灵敏度高、准确性好,可同时测定瑞格列奈和利伐沙班血药浓度,且两药联用时存在一定的药动学相互作用。
[Abstract]:Objective: to establish a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS) method and to determine the concentrations of rivastaben and reaglinide in rat plasma simultaneously. Methods: 54 male wistar rats were randomly divided into two groups: rivastaban group, reaglinide group and combined treatment group, 18 rats in each group. Blood samples were collected at different time points before and after administration of rivastatin. The plasma concentrations of the two drugs were simultaneously determined by HPLC-MS/MS. The chromatographic column was Diamonsil C18 column, the mobile phase was acetonitrile-0.1% formic acid aqueous solution 60: 40, the mass spectrometry condition was electrospray ion source and ESI source, and the positive ion mode detection was used. The scanning mode is multi-reaction monitoring and the ion reaction for quantitative analysis is m / z 436.0. 鈫扢 / z 144.9m / z 452.9. 鈫扢 / z 162.3 and m / z 324.1. 鈫扢 / z 127.2 (the linear range of mass concentration of rivastaben and rieglinide were 12.5U 800 ng 路ml -1 and 0.997 1, respectively) and 2.5 L 160ng 路m L -1 ru 9 9951.Results: compared with the group treated with repaglinide alone, the parameters of repaglinide in the combined drug group did not change significantly. Compared with the group treated with rivastaban alone, the combined treatment group significantly increased AUC0-24 AUC0- 鈭，

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