High-performance liquid chromatographic assay of 5-fluorouracil in human erythrocytes, plasma and whole blood.
A HPLC assay method was modified and validated for the determination of 5-fluorouracil in human red blood cells, plasma and whole blood with a two-fold increased sensitivity (detection limit=10 ng/ml). The assay was linear from 25 to 1500 ng/ml and the accuracy ranged from 96.7 to 103.2% at 25 ng/ml, 94.8 to 99.4% at 500 ng/ml, and 98.9 to 99.5% at 1500 ng/ml. Intra-assay and inter-assay coefficients of variation were less than 8% over the range of concentrations and less than 8% over 10 days of analysis. After intravenous bolus and infusion of 5-fluorouracil in patients with colorectal cancer, the concentrations of 5-fluorouracil in whole blood were 108-111% of plasma concentrations, while packed red blood cells levels were 8-15% of plasma concentrations in the five patients studied. By utilising basic analytical hardware, this represents an accurate, precise, reproducible and affordable method for 5-fluorouracil pharmacokinetics investigation and therapeutic drug monitoring.
Wattanatorn
W
W
School of Pharmacy, The Robert Gordon University, Schoolhill, Aberdeen, UK.
McLeod
H L
HL
Cassidy
J
J
Kendle
K E
KE
D000964:Antimetabolites, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy; D004912:Erythrocytes / Q000737:chemistry*; D005472:Fluorouracil / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D015203:Reproducibility of Results
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil