氟尿嘧啶磁性微球在小鼠体内的药动学  

Pharmacokinetics of 5-fluorouracil-magnetic micropheres in mice

作　　者：师少军[1] 徐戎[2] 李忠芳[3] 陈汇[2] 陈华庭[1] 曾繁典[2] 

机构地区：[1]华中科技大学同济医学院附属协和医院药剂科,湖北武汉430022 [2]华中科技大学同济医学院临床药理研究所,湖北武汉430030 [3]华中科技大学同济医学院附属协和医院妇产科,湖北武汉430022

出　　处：《中国医院药学杂志》2008年第5期333-335,共3页Chinese Journal of Hospital Pharmacy

基　　金：国家科技部863课题(编号:2002AA214061)

摘　　要：目的：建立高效液相色谱法测定磁性微球中氟尿嘧啶（5-Fu）农度，研究5-Fu及其磁性微球在小鼠体内的药动学。方法：采用Hypersil C18柱（4．6mm×150mm，5μm），流动相为乙腈-水（含0．25％醋酸）（3：97），检测波长265nm，样品经醋酸乙酯萃取后测定，数据应用DAS程序拟合。结果：血浆5-Fu在0．1～50mg·L^-1。质量浓度范围内线性关系良好（r=0．9999），血浆最低检测质量浓度为0．1mg·L^-1，日内及日阅RSD分别小于1．63％，2．13％，方法回收率为102．56％～103．20％，平均提取回收率大于80％。小鼠静脉注射5-Fu及其磁性微球的药-时曲线符合二房室开放模型，二者主要药动学参数C0、AUC、t1/2β、MRT、Vd、CL差异具有显著性。结论：5-Fu制备成磁性微球后在小鼠体内药动学行为发生了明显改变，具有明显的缓释作用，有效作用时间延长，更有利于其抗肿瘤作用。OBJECTIVE To establish an HPLC method for the determination of 5-fluorouraciI（5-Fu）in magnetic micropheres （MMS） ,and to study the pharmacokinetics of 5-Fu and its magnetic micropheres （5-Fu-MMS） in mice. METHOI）S 5-Fu was extracted from plasma with ethyl acetate,and then determined by Hypersil C18 column （4. 6 mm× 150mm,5μm） with UV detection at 265 nm. The mobile phase consisted of acetonitrile-water （0. 25% acetic acid） （3：97） with a flow rate of 1.0 mL·min^-1. RESULTS The calibration curve was linear over the range of 0.1-50 mg·L^-1 （r= 0. 999 9） and the limit of quantitation was 0. 1 mg·L^-1. The intra- and interday assay coefficients of variation were less than 1. 63% and 2.13%, respectively. The mean analytical recoveries were 102. 56%-103.20%,and the mean extraction recoveries were all more than 80~. Plasma concentration-time profiles of 5-Fu and 5-Fu-MMS were adequately described by a two-compartment open model. There were statistically significant differences existed in main pharmacokinetic parameters Co,AUC,t1/2β,MRT,Vd and CL. CONCLUSION The results idicate that the MMS preparation can change 5-Fu pharmacokinetics behavior. 5-Fu-MMS has slow-release effect,which is helpful for the antitumor therapy of 5-Fu.

关 键 词：氟尿嘧啶 磁性微球 高效液相色谱法 药动学 

分 类 号：R969.1[医药卫生—药理学]