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Quantitation of 5‐fluorouracil (5‐FU) in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry

2007; Wiley; Volume: 22; Issue: 2 Linguagem: Inglês

10.1002/rcm.3362

1097-0231

Juliann E. Kosovec, Merrill J. Egorin, Susanna Gjurich, Jan H. Beumer,

Neutropenia and Cancer Infections

Abstract 5‐Fluorouracil (5‐FU) has long had a place in the treatment of many malignancies. 5‐FU plasma concentrations have been correlated with toxicity and efficacy, and therapeutic drug monitoring has been reported to result in an improved response/toxicity balance. We report validation, according to FDA guidelines, of a hydrophilic interaction chromatography (HILIC) liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay for the sensitive, accurate and precise quantitation of 5‐FU in human plasma. The assay employed an isotopically labeled 5‐FU internal standard and ethyl acetate extraction. Separation was achieved with an amino column and an isocratic mobile phase of 0.1% formic acid in acetonitrile/water (97:3, v/v), followed by a wash. Detection consisted of electrospray, negative‐mode ionization tandem mass spectrometry in the multiple reaction monitoring (MRM) mode. The accuracy was 96.0–102.2%, and precision was 2.1–7.5% in the concentration range of 10–10 000 ng/mL. Recovery from plasma was 46.0–72.6%, and ion suppression was 9.8–25.7%. Plasma freeze/thaw stability was 87.5–104.3%, and stability for 4 h at room temperature was 98.7–100.0%. This assay is currently being used to quantitate 5‐FU in human plasma samples. Copyright © 2007 John Wiley & Sons, Ltd.