【摘要】 目的:建立 Beagle 犬血浆中3,4-O-异亚丙基莽草酸（ISA）的 RP-HPLC 分析方法,并对 ISA 原料药静注给药在犬体内药动学过程进行分析研究。方法:犬血浆样品中加入内标物芦丁,采用酸性甲醇沉淀蛋白质并提取药物,采用 RP-HPLC法测定。大连依利特 Hypersil ODS 2柱（250 mm×4.6 mm,5μm）;流动相:甲醇-0.3%醋酸（50:65）;检测波长:220 nm;柱温:室温;流速:1.0 mL·min^-1。动物实验使用 Beagle 犬6只,采用静脉注射给药(200 mg·kg^-1),进行血药浓度测定。结果:犬血浆样品中 ISA 无干扰,以芦丁为内标,测定血药浓度最低检测限3 ng·mL^-1;ISA 浓度在0.01～600μg·mL^-1范围内对ISA 峰面积和内标峰面积的比有较好的线性关系,r=0.9996,绝对回收率大于70%,方法回收率在98.5%～103.3%之间;日内精密度、日间精密度 RSD 分别小于5%和15%。ISA 原料药静脉注射在犬体内过程符合二室模型。结论:本法准确、灵敏度较高,可用于 ISA 体内过程的研究。更多还原

【Abstract】 Objective:To establish an RP-HPLC method for the study of pharmacokinetics of 3,4-oxo-isoprop- ylidene-shikimic acid（ISA）in Beagle dog.Method:Rutin was used as internal standard.After adding rutin,the dog plasma samples were extracted with the mobile phase and determined by RP-HPLC.The separation was car- ried out on a Hypersil ODS 2 column（250 mm×4.6 ram,5μm）,the mobile phase was methanol-0.03% acetic acid（50:65）and detection at 220 nm,running at a flow rate of 1.0 mL·min^-1.Blood samples were obtained at 0,5,10,15,20,25,30,40,60,80,120,180,240,300,360,480,600 min after intravenous infusion of 200 mg· kg^-1.Results:ISA was separated completely without interference.The peak area of ISA showed good linearity within the range 0.01-600 μg·mL^-1,r=0.9996.The LOD of ISA in plasma was 3 ng·mL^-1.The extraction recovery was more than 70%,the method recovery was 98.5%-103.3%.The within-and between-day RSD was less than 5% and 15% respectively.Conclusion:This method is simple and sensitive with good recovery,and can be used in analyzing ISA in plasma sample.更多还原