Sensitive liquid chromatographic assay for the simultaneous determination of 5-fluorouracil and its prodrug, tegafur, in beagle dog plasma.
A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of 5-fluorouracil (5-FU) and its prodrug, tegafur (TF), in dog plasma. 5-FU, the internal standard, 5-bromouracil, and TF were separated on a C18 Spherisorb ODS2 column using isocratic elution with retention times of 4.4, 8.0 and 21.2 min, respectively. Detection by UV absorption at 260 nm gave a limit of quantitation of 4 microg/l for 5-FU in plasma. Calibration curves for 5-FU and TF were linear over the ranges of 4-160 microg/l and 0.48-19.2 mg/l, respectively. Intra- and inter-day precision over these concentration ranges were <10.9 and <13.6% for 5-FU and TF, respectively, with good accuracy for both compounds. The method was successfully applied to define plasma concentration-time curves of TF and 5-FU in dogs administered a single oral dose containing TF (100 mg) and uracil (224 mg).
Chu
Dafeng
D
Research Center for Drug Metabolism, Jilin University, Changchun 130023, China.
Gu
Jingkai
J
Liu
Wanhui
W
Paul Fawcett
J
J
Dong
Qingguang
Q
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D005472:Fluorouracil / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D005641:Tegafur / Q000097:blood*
D000964:Antimetabolites, Antineoplastic; D005641:Tegafur; D005472:Fluorouracil