【作者】 郭孟楠； 董燕； 纪庆月； 梁明杰； 刘丹； 刘茜；

【Author】 GUO Meng-nan1,DONG Yan2,JI Qing-yue1,LIANG Ming-jie1,LIU Dan1,LIU Qian1 (1. School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;2. Shanxi Cardiovascular Hospital,Shanxi 030000,China)

【机构】 沈阳药科大学药学院； 山西省心血管病医院；

【摘要】 目的:建立测定大鼠血浆中米格列奈的LC-MS/MS法,并用于考察联合使用阿托伐他汀后米格列奈在大鼠体内药动学行为的改变。方法 :12只健康雄性SD大鼠随机分成两组(分别为单独和联合给药组),采用LC-MS/MS法测定血浆中米格列奈的浓度。色谱柱:SunFireC18柱,流动相:乙腈-水-甲酸(体积比为70.0∶30.0∶0.3),质谱检测采用多反应监测模式(multiplereactionmonitoring,MRM),电喷雾离子源,分析时间:1.8min。。结果 :大鼠单独灌胃给予米格列奈组与联合阿托伐他汀组主要的的药动学参数:ρmax分别为(1229±388)和(1341±598)mg·L-1,Tmax分别为(0.21±0.04)和(0.61±0.25)h,t1/2分别为(1.76±0.62)和(1.19±0.23)h,AUC0-t分别为(1974±452)和(3010±1307)mg·h·L-1,AUC0-∞分别为(2138±433)和(3098±1321)mg·h·L-1,Tmax具有显著性差异(p<0.05),其它药动学参数均无显著性差异(p>0.05)。结论 :联合用药后米格列奈达峰时间明显推迟,Tmax由0.21±0.04h推迟为0.61±0.25h。作为餐食血糖调节剂的米格列奈优点是其给药后起效迅速作用时间短,联合用药后推迟了米格列奈起效时间,提示临床两药联用时应注意避免同时口服米格列奈和阿托伐他汀,尽量分开时间服用,以保证米格列奈起效迅速的降糖效果。更多还原

【Abstract】 Objective To establish a LC-MS/MS method for determination of mitiglinide in rats plasma,and investigate the effect of atorvastatin on pharmacokinetics of mitiglinide.Method 12 healthy male SD rats were divided into two groups (i.g.administration to mitiglinide alone and combination of atorvastatin and mitiglinide).The concentration of mitiglinide in plasma was determined by LC-MS/MS.The chromatographic separation was performed on a Sun Fire C18 column with a mobile phase of acetonitrile-water-formic acid solution(70:30:0.3,v/v/v).Analytes were detected with an API2000 triple quadrupole mass spectrometer equipped with an electrospray ionization source.The analysis time is 1.8 min.Results The main pharmacokinetics parameters of single and combination administration groups were as follow: ρmax were (1229±388) and (1341±598) mg·L-1,Tmax were (0.21±0.04) and (0.61±0.25) h,t1/2 were (1.76±0.62) and (1.19±0.23) h,AUC0-t were (1974±452) and (3010±1307) mg·h·L-1;AUC0-∞ were (2138±433) and (3098±1321) mg·h·L-1.Significant difference was found on Tmax (p <0.05).Conclusion The Tmax of mitiglinide in rat can be put off after together administration with atorvastatin.Tmax changed from 0.21±0.04 h into 0.61±0.25 h.The advantage of mitiglinide are rapid onset and short duration.Atorvastatin have significant effect on the tissue distribution in mice of mitiglinide.More attention should be paid to the two drugs when mitiglinide and atorvastatin were used at the same time in clinical.To ensure mitiglinide onset of hypoglycemic effect ,we should separate the taking time of those two drug’s.更多还原