Determination of the concentrations of 5-fluorouracil and its metabolites in rabbit plasma and tissues by high-performance liquid chromatography

The concentrations of 5-fluorouracil, 5-fluoro-5,6-dihydrouracil, 5-fluorouridine and 5-fluoro-2'-deoxyuridine in plasma, liver, kidney, lung and heart of rabbits were determined by high-performance liquid chromatography (HPLC) after drug administration by two different routes. HPLC was carried out by using a Spherisorb 5 ODS 2 column and 0.05 M phosphate buffer as the mobile phase with UV detection at 200 nm. The pH of the mobile phase, organic modifier content and column temperature were found to have a profound influence on the results, hence it was necessary to optimize a procedure for each matrix. A comparison of the efficiency of intravenous and peritoneal administration revealed that the latter provides higher drug concentrations in the liver and minimal contents in plasma and all other tissues studied.