Determination of 5-fluorouracil and its main metabolites in plasma by high-performance liquid chromatography: Application to a pharmacokinetic study

被引:35
作者
Joulia, JM
Pinguet, F
Grosse, PY
Astre, C
Bressolle, F
机构
[1] CTR REG LUTTE CONTRE CANC,LAB ONCOPHARMACOL,F-34094 MONTPELLIER,FRANCE
[2] FAC PHARM MONTPELLIER,LAB PHARMACOCINET,F-34060 MONTPELLIER 01,FRANCE
来源
JOURNAL OF CHROMATOGRAPHY B | 1997年 / 692卷 / 02期
关键词
5-fluorouracil; 5-fluorouridine; 5-fluoro-2'-deoxyuridine;
D O I
10.1016/S0378-4347(96)00518-X
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 C-18 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.
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页码:427 / 435
页数:9
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