High-performance liquid chromatographic determination of 5-fluorouracil and its prodrugs, tegafur and 4-deoxy-5-fluorouracil, in rat plasma.
A rapid, sensitive and reproducible ion-pair, reversed-phase high-performance liquid chromatographic (HPLC) method was developed to simultaneously quantitate 5-fluorouracil (5FU) and its prodrugs, tegafur (TF) and 4-deoxy-5-fluorouracil (DFU), in rat plasma. 5FU, TF, and internal standard 2', 3'-didehydro-2'-deoxythymidine (D4T, stavudine), were detected by UV absorption at 254 nm, and DFU was detected at 313 nm. Extraction recoveries for all compounds ranged between 80% and 92%. Retention times of 5FU, D4T, DFU and TF were 4.6, 5.5, 6.8 and 11.5 min, respectively. Calibration plots were linear over the range of 0.1 microgram/ml to 50 micrograms/ml for 5FU, and 0.25 microgram/ml to 50 micrograms/ml for TF and DFU. The limit of quantitation was 0.1 microgram/ml for 5FU and 0.25 microgram/ml for TF and DFU. The intra- and inter-day variations were less than 10% and accuracy was greater than 90%. This method was applied to plasma samples collected from rats that were administered 5FU, TF and DFU intravenously.
Jarugula
V R
VR
Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602, USA.
Boudinot
F D
FD
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics; D001711:Biotransformation; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000493:pharmacokinetics*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D005641:Tegafur / Q000097:blood* / Q000493:pharmacokinetics
C101558:4-deoxy-5-fluorouracil; D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D005641:Tegafur; D005472:Fluorouracil