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利伐沙班和瑞格列奈在大鼠體內(nèi)藥動學(xué)相互作用

發(fā)布時間:2018-03-18 23:36

  本文選題:高效液相色譜-串聯(lián)質(zhì)譜 切入點:利伐沙班 出處:《中國新藥雜志》2017年06期  論文類型:期刊論文


【摘要】:目的:建立高效液相色譜-串聯(lián)質(zhì)譜(HPLC-MS/MS)法,同時測定大鼠血漿中利伐沙班和瑞格列奈濃度,并初步考察兩藥的藥動學(xué)相互作用。方法:將54只雄性wistar大鼠隨機分為單用利伐沙班組、單用瑞格列奈組和聯(lián)合用藥組,每組18只,于給藥前后不同時間點眼內(nèi)眥采集血樣,采用HPLC-MS/MS法同時測定兩藥的血藥濃度。色譜柱為Diamonsil C18柱,流動相為乙腈-0.1%甲酸水溶液(60∶40),質(zhì)譜條件為電噴霧離子源(ESI源),正離子模式檢測,掃描方式為多反應(yīng)監(jiān)測(MRM),用于定量分析的離子反應(yīng)分別為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(格列齊特)。利伐沙班、瑞格列奈檢測質(zhì)量濃度線性范圍分別為12.5~800 ng·m L-1(r=0.997 1)和2.5~160 ng·m L-1(r=9 995)。結(jié)果:與單用瑞格列奈組相比,聯(lián)合用藥組瑞格列奈各項參數(shù)沒有顯著變化;與單用利伐沙班組相比,聯(lián)合用藥組利伐沙班AUC0-24,AUC0-∞和Cmax明顯增大(P0.05),清除率(CL)明顯減小(P0.05)。結(jié)論:該方法專屬性強、靈敏度高、準(zhǔn)確性好,可同時測定瑞格列奈和利伐沙班血藥濃度,且兩藥聯(lián)用時存在一定的藥動學(xué)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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