Influence of Puncture Devices on the Accuracy of Cyclophosphamide Dosing for Chemotherapy Administration

Abstract

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.

Keywords: anticancer drugs; aspiration devices; chemotherapy preparation; cyclophosphamide; dose accuracy; high-performance liquid chromatography with diode-array detection (HPLC-DAD); quality control.

Figure 1

HPLC-DAD chromatogram of a 400 µg/mL cyclophosphamide standard solution.

Figure 2

Cyclophosphamide calibration curve (10–400 µg/mL).

Figure 3

HPLC-DAD chromatograms of a 50 µg/mL cyclophosphamide standard solution (A) and a 50 µg/mL cyclophosphamide, paclitaxel and 5-FU standard solution (B).

Figure 4

Cyclophosphamide concentration in samples taken from the same vial by operators A and B, using either a needle or spike A. The red line indicates theoretical concentration (200 µg/mL).

Figure 5

Cyclophosphamide concentration in samples taken from the same vial by operators C and D using either a needle or spike B. The red line indicates the theoretical concentration (200 µg/mL).

Figure 6

Withdrawal of cyclophosphamide solution from the vial, with the needle tip positioned near the elastomer (highlighted).

Figure 7

Representative figures of cyclophosphamide solution withdrawing using an 18G needle (I), spike A (II) and spike B (III) as puncture devices.