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J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Apr 15;879(13-14):915-20. doi: 10.1016/j.jchromb.2011.02.045. Epub 2011 Mar 5.

The achievement of mass balance by simultaneous quantification of floxuridine prodrug, floxuridine, 5-fluorouracil, 5-dihydrouracil, α-fluoro-β-ureidopropionate, α-fluoro-β-alanine using LC-MS.

Author information

1
Department of Pharmaceutical Science, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA.

Abstract

5-Fluoro-2'-deoxyuridine (floxuridine, 5-FdUrd) and 5-fluorouracil (5-FU) are widely used for the treatment of colorectal cancers. The mechanisms of action of 5-FdUrd and 5-FU, as well as the biochemical pathway responsible for their metabolism, are well understood. Identification of every metabolite and achieving mass balance by conventional UV absorption-based HPLC analysis are not feasible because the metabolites beyond 5-FU in the 5-FdUrd metabolic pathway are undetectable by UV light. We therefore established a mass spectrometry method, designed for fast and convenient analysis, for simultaneously measuring 5-FdUrd, 5-FU, and their metabolites. Linearity, precision and accuracy were validated in the concentration ranges studied for each compound. Hydrolysis studies of 5-FdUrd and amino acid mono ester prodrugs of 5-FdUrd in Capan-2 cell homogenates were carried out and the achievement of mass balance was established with this method (recovery of 5'-O-l-leucyl-FdUrd was 96.6-108.2% and that of 5-FdUrd was 79.4-117.4%). This simple LC-MS method achieves reliable quantitation and mass balance of 5-FdUrd, 5-FU, and their metabolites and can be effectively utilized for further kinetic studies.

PMID:
21450537
PMCID:
PMC3086577
DOI:
10.1016/j.jchromb.2011.02.045
[Indexed for MEDLINE]
Free PMC Article

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