A new minor metabolite of 5-fluorocytosine, 5-hydroxy-5-fluorocytosine, was found in the urinary gravel excreted by a patient being treated with this drug. A metabolite of 5-fluorocytosine in animals, alpha-fluoro-beta-alanine, was identified and quantitated in the urine of nine patients. In general, alpha-fluoro-beta-alanine represented 0.05--0.25% of the daily dose of 5-fluorocytosine, both for orally and intravenously administered drug. Minor metabolites have been implicated in the occasional toxicity observed in patients receiving 5-fluorocytosine.
Isobutane chemical ionization gas chromatography mass spectometry of the N-trifluoroacetyl-carboxy-n-butyl ester derivatives of amino acids, using a commercial per-13C-amino acid mixture as internal standards, provided a sensitive and specific method for quantitative analysis of fourteen urinary alpha-amino acids. A computer controlled quadrupole mass spectrometer was used in a selected ion monitoring mode to record the ion current due to the protonated molecular ions of each alpha-amino acid/13C analogue pair. BASIC programmes located peak maxima, and using previously established standard curves, calculated the amino acid content on the bases of both peak height and peak area ratios. Duplicate amino acid analyses are possible on 5 microliter of urine. Instrumental analysis required 25 minutes, automated data processing 10 minutes, and sample preparation 2 hours. Detection limits approached 1 ng with a typical mean standard deviation of 2% for the instrumental analysis.
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