Journal of Chromatography B 2003-07-05

Sensitive method for the quantification of urinary pyrimidine metabolites in healthy adults by gas chromatography-tandem mass spectrometry.

Ute Hofmann, Matthias Schwab, Sonja Seefried, Claudia Marx, Ulrich M Zanger, Michel Eichelbaum, Thomas E Mürdter

Index: J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 791(1-2) , 371-80, (2003)

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Abstract

Enzyme deficiencies in pyrimidine metabolism are associated with a risk for severe toxicity against the antineoplastic agent 5-fluorouracil. To assess whether urinary levels of pyrimidines and their metabolites can be used for predicting patients' individual phenotype, a new gas chromatographic-tandem mass spectrometric method was developed which allows the simultaneous determination of uracil and thymine and their metabolites dihydrouracil, dihydrothymine, beta-ureidopropionic acid, beta-ureidoisobutyric acid, and the amino acids beta-alanine and beta-aminoisobutyric acid in human urine. Small aliquots (2-20 microl) of the urine samples were evaporated and derivatized to the tert.-butyldimethylsilyl derivatives before quantification, using the respective stable isotope-labelled analogues as internal standards. Analytical variation was acceptable with an intra-day imprecision (RSD) below 10%, for beta-ureidoisobutyric acid below 15%. The method was used for investigating the stability of urine samples and the influence of urine collection at different times.