Background/Objectives: Cyclophosphamide is one of the most commonly used cytotoxic drugs in chemotherapy protocols. Its preparation in the hospital setting involves handling concentrated solutions, which pose occupational exposure risks and potential variations in the final dose administered. The aim of this study was to evaluate the effect of aspiration devices on the concentration of cyclophosphamide in reconstituted solutions. Methods: An analytical method was validated using high-performance liquid chromatography coupled to a diode-array detector (HPLC-DAD) for quality control. Cyclophosphamide solutions were prepared and aspirated using either a conventional needle or spike device with or without a filtration system. Results: The validated method demonstrated linearity (R² = 0.9999), high precision (0.22–4.59%) and accuracy (88.9–99.4%), with a limit of quantification of 4.03 µg/mL. Significant differences (p < 0.001) were observed between samples aspirated with a needle and those aspirated with a spike fitted with a 5 µm filter, with the latter showing lower cyclophosphamide concentrations, suggesting partial retention of the drug. No significant differences were found between the needle and filterless spike preparations. Conclusions: These results suggest that the choice of aspiration device influences the final drug concentration, potentially affecting therapeutic efficacy. Standardisation of preparation techniques and an awareness of device limitations are essential to ensure accurate chemotherapy dosing and patient safety.

Background/Objectives: The leakage of 5-fluorouracil (5-FU) from elastomeric infusion pumps used in cancer therapy poses a potential risk of unintentional exposure to multiple individuals, including patients’ relatives and healthcare professionals, and may also compromise the accurate administration of 5-FU dosages to patients. This study aimed to develop, validate, and apply an analytical method to detect and quantify 5-FU residues on the external surfaces of infusion pumps. Methods: A high-performance liquid chromatography with diode-array detection (HPLC-DAD) method was optimized for the quantification of 5-FU contamination across different components of the infusion pump, including the hard casing, infusion tubing, and catheter connection port. A mobile phase containing 5% acetic acid was used to obtain more efficient separation of 5-FU and the detection was performed at 260 nm. The method was evaluated for linearity, sensitivity, precision, accuracy, selectivity, robustness, and stability. Results: The method demonstrated linearity within the range of 0.150 to 3.000 µg/cm², with limits of detection and quantification of 0.05 µg/cm² and 0.14 µg/cm², respectively. Relative standard deviations ranged from 1.8% to 12.7%, and accuracy exceeded 85%. In real sample analysis, detectable residues were found around the catheter connection port. Conclusions: This screening-oriented method addresses an existing gap, as previous contamination reports were based solely on self-reported user observations. The detection of 5-FU residues highlights the critical need for safe handling practices and the consistent use of personal protective equipment (PPE) to protect healthcare workers, especially nursing staff involved in the removal of the infusion pumps, after treatment.