吲哚美辛5-氟尿嘧啶甲酯的代谢物5-氟尿嘧啶在大鼠体内组织分布和排泄  

Tissue distribution and excretion of 5-fluorouracil from indomethacin 5-fluorouracil-1-ylmethylester in rats

作　　者：汪广厚[1] 王晶[1] 齐伟[1] 陈扬[1] 孙立新[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《药学学报》2008年第1期81-85,共5页Acta Pharmaceutica Sinica

摘　　要：采用高效液相色谱法对吲哚美辛5-氟尿嘧啶甲酯（indomethacin5-fluorouraeil-1-ylmethylester，IFM）的代谢物5-氟尿嘧啶在大鼠体内的分布和排泄进行研究。生物样品经液-液萃取后，以甲醇-水-36％乙酸（3：96．9：0．1，v／v）或甲醇-水-36％乙酸（10：89．9：0．1，v／v）为流动相，使用Diamonsi^TM C18色谱柱进行分离，检测波长为260nm。大鼠灌胃IFM100mg·kg^-1后，5-氟尿嘧啶在胃、小肠、肝组织中浓度较高，其他组织和血浆中较低。5-氟尿嘧啶从尿液（0～24h）、粪便（0～48h）中排泄量分别占给药总量的0．0065％和0．063％。该方法准确、专属性强，适用于IFM代谢物5-氟尿嘧啶的临床前药代动力学研究。To study the tissue distribution and excretion of indomethacin 5-fluorouracil-1-ylmethyl ester （IFM） metabolite 5-fluorouracil in rats, an accurate and specific high performance liquid chromatography method for quantifying IFM in rat plasma and tissues was developed. Biological samples were prepared by liquid-liquid extraction and separated on a Diamonsil^TM C18 column （250 mm×4.6 mm ID, 5μm）. The mobile phase for tissue samples, plasma samples and feces samples were composed of methanol-water-36% acetic acid （3 ： 96. 9 ： 0. 1, v/v） and the mobile phase for urine samples was a mixture of methanol-water-36% acetic acid （10：89.9：0. 1, v/v）. The eluate was monitored by UV absorbance at 260 nm. After a single ig dose of 100 mg·kg^- 1 IFM in rats, 5-Fu was mainly distributed in stomach, small intestine, and liver. The concentrations of 5-fluorouracil in other tissues and plasma were low. The excretion of 5-Fu in urine and feces amounted to 0.006 5% and 0.063% of the dose, respectively. The method is shown to be accurate and specific, and suitable for preclinical pharmacokinetlc studies of IFM.

关 键 词：吲哚美辛5-氟尿嘧啶甲酯 5-氟尿嘧啶 HPLC 前体药物 组织分布 排泄 

分 类 号：R917[医药卫生—药物分析学]