UHPLC-MS/MS method for the quantification of ultra-traces of irinotecan and its metabolites in red blood cells and plasma to detect caregivers' contamination.

The occupational exposure of caregivers to antineoplastic agents has been demonstrated since 1979. Since the early 1990s, numerous studies from several countries have demonstrated the contamination of care facilities by antineoplastic drugs. As it is easier to sample, most contamination measurements in workers are carried out in urine sample. The distribution and elimination half-lives of irinotecan suggest that blood can be considered as better than urine for the biomonitoring of a potential contamination of healthcare workers. We describe here the development and the validation of a UHPLC-MS/MS method to simultaneously quantify irinotecan, and two of its main metabolites, APC and SN-38, at ultra-trace levels in plasma and red blood cells (RBC). This method has been applied to blood samples collected from several healthcare services in a French comprehensive cancer center. The results demonstrate that the method is sensitive enough to identify a contamination of healthcare workers by irinotecan and SN-38 at very low concentrations. Moreover, the results show that analysis of RBC is of great interest and complementary to that of serum.

Blood contamination of the pharmaceutical staff by irinotecan and its two major metabolites inside and outside a compounding unit.

BACKGROUND: Caregivers in healthcare settings are exposed to a risk of antineoplastic drug contamination which can lead to adverse health effects. Biological monitoring is necessary to estimate the actual level of exposure of these workers. This study was conducted with the aim of assessing blood contamination levels by irinotecan and its metabolites of pharmaceutical staff operating inside and outside a compounding unit. METHODS: The study took place within the pharmaceutical unit of a French comprehensive cancer centre. Blood samples were collected from the pharmacy workers operating inside and outside the compounding unit, and analysed by UHPLC-MS/MS. Plasma and red blood cell irinotecan and its metabolites (SN-38; APC) were determined with a validated analytical method detection test. RESULTS: A total of 17/78 (21.8%) plasma and red blood cell-based assays were found to be contaminated among staff. Overall, the total number of positive assays was significantly higher for staff members working outside the compounding unit than for workers working inside it (P = 0.022), with respectively 5/42 (11.9%) and 12/36 (33.3%) positive assays. For plasma dosages, the "outside" group had a significantly higher number of positive assays (P = 0.014). For red blood cell-based assays, no significant difference was found (P = 0.309). CONCLUSIONS: This study reveals that pharmaceutical staff serving in health care settings are exposed to a risk of antineoplastic drug contamination, not only inside the compounding room but also in adjacent rooms. The results would help to raise awareness and potentially establish protective measures for caregivers working in areas close to the compounding room as well.

Is hyperthermic intraperitoneal chemotherapy (HIPEC) safe for healthcare workers?

BACKGROUND: During hyperthermic intraperitoneal chemotherapy (HIPEC), caregivers are exposed by different routes to cytotoxic drugs. This review proposes an overview of the safety of HIPEC by assessing existing data on protection procedures, biological and non-biological samples. Based on these data, relevant good practices, eventual irrelevant overprotection procedures and missing data to implement adapted protections are highlighted. MATERIALS AND METHODS: Data were extracted from a systematic review of literature from 1980 till 2016: number and type of surgical procedure, healthcare professionals present, protective equipment, samples, pre-analytical method and analytical method. RESULTS AND DISCUSSION: Only 55 HIPEC procedures have been evaluated. The majority of antineoplastic drugs used have all required characteristics to penetrate the organism and are recognized as very dangerous. Moreover, a great heterogeneity in protective equipment used, either individual or collective is observed. Environmental contamination occurs during HIPEC, especially for all surfaces in the operating room. Compounds penetration into caregivers lungs cannot be excluded. Priority remains to prove professionals contamination by focusing on biological samples. Biological material is rarely sampled or samples are not necessarily adapted. CONCLUSION: Repeated blood tests should be preferred using appropriate sampling schedules and validated sensitive analytical methods. Furthermore, there is a great need of new biological indicators to monitor caregivers exposure. During hyperthermic intraperitoneal chemotherapy (HIPEC), healthcare workers are exposed by different routes to cytotoxic drugs. There are currently few available occupational exposure data and environmental monitoring and biomonitoring must be improved in order to ensure optimal protection against antineoplastic drugs.