Validation of a novel [2-13C]-uracil breath test (UraBT) to detect dihydropyrimidine dehydrogenase (DPD) deficiency by LC-MS-MS analysis of [2-13C]-uracil (URA) and [2-13C]-dihydrouracil (DHU) plasma levels

2130 Background: DPD deficiency is a pharmacogenetic syndrome which occurs in approximately 5–7 % of cancer patients as potentially lethal 5-fluorouracil (FU) toxicity. Currently, there are no clinically feasible assays to routinely screen prior to FU administration. We recently reported a novel breath test (UraBT) to rapidly detect partially (PDef) and completely (CDef) DPD deficient individuals. * Objective: Determine if plasma URA and DHU correlate with 13CO2 breath levels obtained from healthy or DPD deficient subjects. Methods: 13CO2 breath levels from 10 healthy, 9 PDef and 1 CDef subjects were determined by infrared spectrophotometry using UraBT methodology. * Twelve plasma samples were obtained over 180 min. post URA ingestion; LC-MS-MS quantified URA and DHU plasma levels. Breath (13CO2) and plasma (URA and DHU) levels of the subject groups were analyzed for significance (T and Mann-Whitney U tests). Results: The CDef subject had no detectable plasma DHU with minimal expired 13CO2 (Cmax = 3.6, Tm...