Cytostatics in Indoor Environment: An Update of Analytical Methods

Abstract

Periodic and adequate environmental monitoring programs are crucial to assess and reduce the occupational exposure of healthcare workers to cytostatics. The analytical methods employed should be rapid, reliable, sensitive, standardized, and include multiple compounds. A critical overview of recent overall procedures for surface and air contamination with cytostatics in workplace settings is presented, with a focus on sampling, sample preparation, and instrumental considerations. Limitations are also addressed and some recommendations and advice are provided. Since dermal absorption is the main exposure route, surface contamination is the preferred indicator of biological uptake and its methods have significantly improved. In contrast, cytostatics’ inhalation is rare; thus, air contamination has been poorly studied, with little improvement. Still, some elements of the analytical methods have not been extensively explored, namely: the amount of wetting solution, the extraction procedure, surface chemistry and roughness, recovery studies from specific surfaces, and cytostatics stability (in surfaces and during shipping and storage). Furthermore, complete validation data (including precision, accuracy, and instrumental and method detection limits) and estimation of global uncertainty are still lacking in most studies, thus preventing method comparison and proposal of standardized procedures.

An Improved LC–MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace Surfaces

“…Initially, extraction conditions were only investigated for CYC, DOX, ETO, and PAC, due to their frequent use in current chemotherapy preparations by the hospital unit involved in the study, as well as worldwide; their previous study in the literature; their IARC classification (CYC and ETO are carcinogenic to humans, while DOX is probably carcinogenic to humans). Regarding the extraction solvent, although isopropanol, ethyl acetate, and nitric, formic or hydrochloric acid have been utilized, the most common are water, methanol and ACN [ 15 ]. Since water would not allow the concentration of the sample by solvent evaporation, and methanol promotes PAC hydrolysis, these solvents were ruled out.…”

“…The wipe sampling procedure, similar to most studies, consisted of cleaning a predefined area, in different directions, with a wetted adsorbent material, since a dry sampling medium would have little tendency to extract cytostatics from surfaces. Common materials for this purpose include gauze/wipes/tissues, cellulose filter papers, and swabs [ 15 ]. The decision to utilize gauze was based on their low cost and availability in hospitals.…”

“…The decision to utilize gauze was based on their low cost and availability in hospitals. Regarding the surface desorbing solution, isopropanol, methanol, water, and ACN are the most common [ 15 ]. Water, ethanol, and isopropanol were considered because they are polar solvents (a fundamental requirement for the extraction of polar compounds such as cytostatics), as well as due to their low cost and availability in hospitals, and the fact that they do not pose increased risks for workers or patients.…”

“…Important validation parameters include linearity, precision, accuracy, specificity, sensitivity, and uncertainty. Nevertheless, this is one of the major gaps in this research area since few methods described in the literature present data validation, and their comparison is challenging due to the lack of global uncertainty values associated with the results [ 15 ]. Consequently, limited accurate quantification and exposure risk assessment have been achieved.…”

“…Wipe sampling is generally employed since it is very useful to recover residual contaminants from surfaces, despite the variety of materials or type and volume of desorbing solution used. LC has been the preferred instrumental technique due to its sensibility for simultaneous cytostatic detection, allowing lower detection limits than available alternatives [ 15 ]. Its fast quantification and the low or null volatility of cytostatics are also relevant.…”