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

TY - JOUR

T1 - Instability of uracil in whole blood might affect cancer treatment with fluoropyrimidines

AU - Tybirk, Lea

AU - Hoffmann-Lücke, Elke

AU - Greibe, Eva

N1 - Funding Information: Funding: This work was supported by the Department of Clinical Biochemistry, Aarhus University Hospital, Denmark. Publisher Copyright: © 2022 Elsevier B.V.

PY - 2023/1

Y1 - 2023/1

N2 - Background and aims: 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. Materials and methods: 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. Results: 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). Conclusion: 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.

AB - Background and aims: 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. Materials and methods: 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. Results: 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). Conclusion: 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.

KW - 5-fluorouracil

KW - Dihydropyrimidine dehydrogrenase (DPD) deficiency

KW - Preanalytical

KW - Stability

KW - Uracil

KW - Whole blood

UR - http://www.scopus.com/inward/record.url?scp=85141939973&partnerID=8YFLogxK

U2 - 10.1016/j.cca.2022.10.017

DO - 10.1016/j.cca.2022.10.017

M3 - Journal article

C2 - 36347332

AN - SCOPUS:85141939973

SN - 0009-8981

VL - 538

SP - 87

EP - 90

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

ER -