Rapid determination of uracil in biological fluids at mercury thin film electrode for early detection of potential 5-fluorouracil toxicity due to dihydropyrimidine dehydrogenase deficiency

• Published in: Biosensors & bioelectronics 2024-10, Vol.262, p.116545, Article 116545
• Main Authors: Ashrafi, Amir M., Selcuk, Ozge, Mukherjee, Atripan, Unal, Didem Nur, Kurbanoglu, Sevinc, Uslu, Bengi, Jurica, Jan, Pekarkova, Jana, Richtera, Lukas, Adam, Vojtech
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil-based therapies; Adsorptive stripping voltammetry; Dihydropyrimidine dehydrogenase phenotyping; Mercury thin film electrode; Uracil determination
• ISSN: 0956-5663; 1873-4235; 1873-4235
• DOI: 10.1016/j.bios.2024.116545

Determination of plasma uracil was reported as a method for evaluation of Dihydropyrimidine dehydrogenase (DPD) activity that is highly demanded to ensure the safe administration of 5-fluorouracil (5-FU)-based therapies to cancer patients. This work reports the development of a simple electroanalytical method based on adsorptive stripping square wave voltammetry (AdSWV) at mercury film-coated glassy carbon electrode (MF/GCE) for the highly sensitive determination of uracil in biological fluids that can be used for diagnosis of decreased DPD activity. Due to the formation of the HgII–Uracil complex at the electrode surface, the accuracy of the measurement was not affected by the complicated matrices in biological fluids including human serum, plasma, and urine. The high sensitivity of the developed method results in a low limit of detection (≈1.3 nM) in human plasma samples, falling below the practical cut-off level of 15 ng mL−1 (≈0.14 μM). This threshold concentration is crucial for predicting 5-FU toxicity, as reported in buffer, and ≤1.15% in biological samples), and accuracy (recovery percentage close to 100%).