Quantification of healthcare workers’ exposure to cyclophosphamide, ifosfamide, methotrexate, and 5-fluorouracil by 24-h urine assay: A descriptive pilot study

Abstract

The objective of this pilot study was to determine the frequency of urination and the concentration of four hazardous drugs (cyclophosphamide, ifosfamide, methotrexate, and fluorouracil) in workers' 24-h urine samples in relation to exposure to traces with hazardous drugs. Methods: The study was conducted in three healthcare centers in the region of Montr eal, Quebec, Canada. We recruited healthcare workers (nurses and pharmacy technicians) assigned to the hematology-oncology department. Each participant was asked to collect all urine voided during a 24-h period, to fill out an activity journal documenting tasks performed and to document the use of personal protective equipment. Samples were analyzed for cyclophosphamide, ifosfamide, methotrexate, and alpha-fluoro-beta-alanine (FBAL, the main urinary metabolite of 5-fluorouracil). Drugs were quantified by ultraperformance liquid chromatography-tandem mass spectrometry (positive electrospray MRM mode). Results: Eighteen healthcare workers (10 nurses and 8 technicians) were recruited and provided consent to participate. Urine samples were obtained between 1 September and 30 September 2019. The number of urinations over the 24-h collection period ranged from 3 to 11 per participant. A total of 128 urine samples were analyzed for the 18 workers. All urine samples were negative for the four antineoplastics tested. Conclusion: No traces of cyclophosphamide, ifosfamide, methotrexate, or FBAL were found in the 24-h urine samples of 18 healthcare workers practicing in three healthcare facilities in Quebec. Although it was feasible to collect 24-h urine samples in this research project, it appears unrealistic to do so recurrently as part of a large-scale surveillance program.

Exposure to Antineoplastic Drugs in Occupational Settings: A Systematic Review of Biological Monitoring Data

“…Among those, 37.8% and 33.3% presented internal contamination with CPA and IP, respectively, with the highest median concentration close to the LOQ of the analytical methods. Conversely to the above-mentioned results, other studies failed to detect any concentration of CPA and IP in exposed healthcare workers [ 10 , 13 , 32 , 38 , 40 , 41 , 44 , 45 ]. When biological monitoring was performed on two Belgian pharmacy technicians engaged in CPA preparation with the aid of a robotic system and without appreciable occupational exposure, undetectable levels of CPA could be retrieved in the 24-h urine samples [ 13 ].…”

“…In fact, while 3.9% of samples collected from the work surfaces of the cytostatic preparation and administration units of an Italian hospital had positive results, among 398 healthcare workers with 24-h urine collection, no traces of ADs, including CPA and IP, could be detected. Comparably, Palamini et al [ 32 ] showed no traces of CPA and IP in the 24 h-urine of 18 nurses and pharmacy technicians assigned to the hematology-oncology departments of three Canadian healthcare centers. These results corroborate those previously obtained from 101 workers at the same departments, where no detectable urinary CPA levels could be determined [ 44 ].…”

“…Palamini et al [ 32 ] demonstrated the absence of MTX in the 24-h urine samples of 18 healthcare workers exposed to four ADs (CPA, IP, MTX and 5-Fluorouracil (5-FU). Similarly, in 101 workers exposed to these four drugs, no urine sample had detectable concentrations of any of the compounds evaluated [ 44 ].…”

“…Koller et al [ 41 ] observed the absence of any trace of 5-FU in workers’ urine samples collected before and after their shift, although 100% of the examined surfaces of the oncology ward, including areas dedicated to the pre-administration, administration/patients’ care and handling of patients’ excreta, were contaminated by 5-FU. Poupeau et al [ 44 ] and Palamini et al [ 32 ], in two different studies conducted at the same hospital, showed the absence of traces of hazardous drugs in the urine of 101 and 18 healthcare workers exposed to 4 ADs including 5-FU, respectively. Dugheri et al [ 40 ] made the same observation: among 398 healthcare workers with 24-h urine collection, no traces of FBAL were detected in the urine samples, even though 3.9% of work surfaces examined during the same period had positive results.…”

“…However, a great deal of variability with respect both to AD concentrations (when available), and percentages of positive samples emerged. Some studies reported no drugs determined [ 10 , 13 , 32 , 38 , 39 , 40 , 41 , 44 , 45 ], while others demonstrated that up to 55% of the analyzed urine samples exceeded the LOD [ 2 , 30 , 35 , 36 , 37 , 47 , 48 ]. These results are in line with those retrieved in previous reviews reporting that, even when technical and PPE was used, a remarkable uptake of ADs could be observed, as percentages of positive urinary samples ranged from 0% to 88.9% in the hospital personnel [ 21 ].…”