Instability of uracil in whole blood might affect cancer treatment with fluoropyrimidines

Measurement of plasma uracil is used before cancer treatment with fluoropyrimidines to determine if patients tolerate a full dose. Incorrect preanalytical handling may cause falsely elevated concentration and result in suboptimal cancer treatment. We aimed to examine the stability of uracil in whole blood stored at room temperature (RT) and the effect of centrifugation temperature.

EDTA tubes (6x4 mL) were collected from 25 healthy volunteers. Five samples were stored 0, 1.5, 2, 3, and 4 h at RT and centrifuged at 4 °C. The sixth sample was centrifuged at RT after 1.5 h. Uracil was measured using an in-house LC-MS/MS method.

Storage of whole blood at RT followed by centrifugation at 4 °C caused a rapid increase in uracil concentration. Already after 1.5 h, the mean change (20.5 % (95 % CI: 11.9-29.2 %)) exceeded the maximum permissible difference. Centrifugation at RT instead of 4 °C after 1.5 h resulted in a smaller increase (7.0 % (95 % CI: 0.7-13.4 %)), although not statistically significant (p = 0.0527).

Uracil was unstable in samples processed according to current recommendations. Our data indicates better stability when centrifugation is performed at RT compared with 4 °C but further research into this is necessary.