Determination of 5-Fluorouracil in Dried Blood Spots for Therapeutic Drug Monitoring and Adverse Event Assessment in Breast Cancer Patients.

Background: 5-Fluorouracil (5-FU) is a chemotherapy drug used to treat breast cancer. Monitoring 5-FU levels in blood is essential due to its narrow therapeutic range, high individual variability, nonlinear pharmacokinetics, dosage calculations based on body surface area, and susceptibility to toxicity influenced by individual factors such as enzyme polymorphisms. Methods: An observational study was conducted in 2 types of patients: patients receiving intravenous 5-FU chemotherapy and those receiving oral chemotherapy with capecitabine as the 5-FU prodrug. 5-Fluorouracil blood levels in those patients were monitored using dried blood spots (DBS) as a biosampling method to correlate them with adverse events experienced by patients. Samples from DBS were analyzed using LC-MSMS which has been fully validated with propylthiouracil as an internal standard. All patients were also interviewed to determine adverse events experienced during 5-FU treatment. These adverse events were evaluated based on Common Terminology Criteria for Adverse Events version 5.0. Results: Among the five patients who received intravenous 5-FU, only one patient had concentrations within the target range of 2-3 µg/mL, two patients were below the target range, and two patients were slightly above the target range. For the patients receiving oral capecitabine, 5-FU concentrations were detectable in only 3 out of 8 patients, with values near the LLOQ. The most common adverse events observed in intravenous chemotherapy patients were constipation, fatigue, and alopecia. Hand-foot syndrome was the most common syndrome in patients receiving oral chemotherapy. Conclusion: The validated DBS method can be applied for therapeutic drug monitoring of 5-FU, offering advantages such as reduced invasiveness compared to traditional venipuncture. However, no significant relationship was found between the administered drug dosage, 5-FU blood levels, and adverse events. This study's limitations include its small sample size, which requires further research with larger cohorts to validate these observations and their clinical relevance.