[Tissue distribution and excretion of 5-fluorouracil from indomethacin 5-fluorouracil-1-ylmethylester in rats].
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 C18 column (250 mm x 4.6 mm ID, 5 microm). 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 x 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 0.0065% and 0.063% of the dose, respectively. The method is shown to be accurate and specific, and suitable for preclinical pharmacokinetic studies of IFM.
Wang
Guang-Hou
GH
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Wang
Jing
J
Qi
Wei
W
Chen
Yang
Y
Sun
Li-Xin
LX
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000652:urine; D005243:Feces / Q000737:chemistry; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000652:urine; D007213:Indomethacin / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D008297:Male; D011355:Prodrugs / Q000493:pharmacokinetics*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D005472:Fluorouracil; D007213:Indomethacin