Purpose: The purpose of this study was to quantify the urine concentration of non-metabolized cyclophosphamide (CP), a commonly administered antineoplastic drug, among potentially exposed Canadian healthcare workers and to identify factors associated with the drug concentration levels.
Methods: Participants were asked to provide two sets of 24-h urine samples (at two different sampling events), and the level of CP was quantified using high-performance liquid chromatography-tandem mass spectrometry. In addition to demographic information, participants were surveyed regarding their frequency of handling of antineoplastic drugs, safe drug handling training, and known contact with CP on their work shift. Descriptive and inferential statistical analyses were performed. A backward stepwise linear mixed effect model was conducted to identify the factors associated with urine concentration levels.
Results: We collected 201 urine samples, and 55 % (n = 111) had levels greater than the LOD of 0.05 ng/mL. The mean urinary CP concentration was 0.156 ng/mL, the geometric mean was 0.067 ng/mL, the geometric standard deviation was 3.18, the 75th percentile was 0.129 ng/mL, and the range was <LOD to 2.37 ng/mL. All eight job categories evaluated had some urinary concentrations in excess of the LOD with unit clerks having the highest average level. Workers who worked in the drug administration unit, but were not responsible for administering the drugs to patients, i.e., volunteers, oncologists, ward aides, and dieticians, had the largest proportion of samples exceeding the LOD. We did not find any correlation between the urinary concentration levels and known contact with CP during the work shift. Two factors were found to be significantly associated with urinary CP concentration: (1) Workers who had a duty to handle antineoplastic drugs had higher concentration levels, and (2) workers who had not received safe drug handling training had higher levels of CP in their urine compared with those who had.
Conclusions: The presence of non-metabolized CP in urine confirms that, despite the existence of control measures, a broad range of healthcare workers are at risk of exposure to antineoplastic drugs. A review of the effectiveness of interventions to reduce exposure is warranted and should apply to all healthcare workers involved in some capacity with the hospital medication system. This study identified two factors that are related to the urine CP concentration levels which can serve as an impetus for reducing exposure.
Keywords: Antineoplastic drugs; Healthcare workers; Hospital medication system; Risk assessment; Urinary concentration.