Determination of 5-fluorouracil and its main metabolites in plasma by high-performance liquid chromatography: application to a pharmacokinetic study.
This paper describes a relatively simple and sensitive high-performance liquid chromatographic assay (HPLC) with ultraviolet absorbance detection for 5-fluorouracil (5-FUra) and its two main metabolites, 5-fluorouridine (5-FUrd) and 5-fluoro-2'-deoxyuridine (5-FdUrd), in plasma. In this study, two plasma clean-up procedures involving addition of internal standard, solid-phase and liquid-liquid extractions have been developed. A reversed-phase Kromasil C18 column was used. The detection was performed at 268 nm for 5-FUra and at 275 nm for the two metabolites. Linear detection responses were obtained for concentrations ranging from 25 to 1000 ng/ml. The average recovery from plasma was 35, 42 and 48% for 5-FUra, 5-FUrd and 5-FdUrd, respectively. Precision, expressed as C.V., ranged from 2.7 to 13% and the mean recovery from 94 to 105%. The limits of quantitation and detection of the three analytes were 20 and 10 ng/ml, respectively. The method was used to monitor the pharmacokinetic profile of 5-FUra and its two metabolites in patients with metastatic colorectal cancer.
Joulia
J M
JM
Laboratoire d'Onco-Pharmacologie, Centre Régional de Lutte Contre le Cancer, Montpellier, France.
Pinguet
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F
Grosse
P Y
PY
Astre
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C
Bressolle
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F
D000964:Antimetabolites, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005472:Fluorouracil / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil