Monitoring of occupational exposure to antineoplastic drugs

Abstract: Antineoplastic drugs are commonly used in the medical treatment of cancer and some other diseases. Workplaces e.g. hospital pharmacies and wards where antineoplastic drugs are used are contaminated with these drugs and health care workers are therefore at risk of getting occupationally exposed. Many antineoplastic drugs are classified as carcinogenic and teratogenic to humans. Cyclophosphamide (CP) and ifosfamide (IF) are two common antineoplastic drugs. The general aim of this thesis was to develop and evaluate methods for monitoring of exposure to antineoplastic drugs. Methods for determination of surface contamination and air sampling, both as vapour and particulates, were developed and validated. Furthermore, methods for determination of antineoplastic drugs in urine and plasma were developed and validated. Analysis was performed by liquid chromatography combined with tandem mass spectrometry. The developed methods had high precisions, sensitivities and specificities and were applicable for monitoring of the exposure at workplaces where antineoplastic drugs are used. To fully validate the biomarker CP in urine, renal clearance of CP was investigated at low plasma and urine concentrations relevant for occupational exposure to CP. This was performed by studying patients treated with CP up to 12 days after the dose. There was no dependence between the plasma concentration and the renal clearance and, thus, CP in urine can be continued to be used as a biomarker of exposure to CP. External contamination on primary packaging containing CP was evaluated and only low amounts of CP and IF were quantified. Furthermore, surface contamination in a hospital pharmacy and three oncology wards was evaluated. The contaminations were generally low but high amounts were detected on the floors in patient lavatories. No CP or IF was detected in urine from personnel in the studied workplaces, although the cleaners and the assistant nurses did not use adequate personal protective equipment (PPE). The variations of surface contamination seemed to be rather low. A risk evaluation of occupational exposure to CP in Sweden was performed. Thus, the occupational exposure for cleaners and assistant nurses constitutes a low but not neglectable lifetime cancer risk. The risk of reproduction effects cannot be excluded since there is a risk of accidental exposure during pregnancy. Thus, it is important for these personnel groups to use adequate PPE such as gloves impermeable to antineoplastic drugs and long-sleeved protective gowns. Information and education are also important.