Simple and sensitive determination of 5-fluorouracil in plasma by high-performance liquid chromatography. Application to clinical pharmacokinetic studies.
5-Fluorouracil (5-FU) is an antineoplastic agent widely employed in the treatment of many types of cancer. Recent studies have proved the need for individual adjustment of 5-FU dosage based on pharmacokinetics. A simple and sensitive high-performance liquid chromatographic method for the determination of 5-FU in plasma and their preliminary clinical pharmacokinetics is described. After sample acidification with 20 microl of orthophosphoric acid (5%), the drug is extracted from plasma using n-propanol-diethyl ether (16:84). The organic layer is evaporated to dryness, the residue dissolved in 100 microl of mobile phase and 20 microl of this mixture is injected into a LiChrospher 100RP-18 (5 microm, 250 x 4.0 mm) analytical column. Mobile phase consisted of potassium dihydrogenphosphate (0.05 M, adjusted to pH 3). The limit of quantitation was 2 ng/ml. The method showed good precision: the within-day relative standard deviation (RSD) for 5-FU (10-20,000 ng/ml) was 3.75% (2.57-5.93); the between-day RSD for 5-FU, in the previously described range, was 5.74% (4.35-7.20). The method presented here is accurate, precise and sensitive and it has been successfully applied for 5-FU pharmacokinetic investigation and therapeutic drug monitoring.
Escoriaza
J
J
Servicio de Farmacia, Clińica Universitaria de Navarra c/Pío XII s/n, Pamplona, Spain.
Aldaz
A
A
Calvo
E
E
Giráldez
J
J
D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011786:Quality Control; D012680:Sensitivity and Specificity; D012997:Solvents
D012997:Solvents; D005472:Fluorouracil