Preliminary analysis for the validation of cross contamination

There is a high risk of cross contamination in the preparation of cytotoxics given the simultaneous handling of numerous molecules of different physical and chemical characteristics in one and the same production zone. Our objective was to perform a preliminary analysis of the physical and chemical characteristics of the active principles handled to propose non-cytotoxic tracers.

The review of cytotoxics was performed with a bibliographic search and examination of the Toxnet® and Drugbank® data bases. A concomitant analysis of the volumes and frequency of handling was also performed. The physical and chemical characteristics selected as being likely to foster cross contamination were low solubility, the octanol/water split coefficient reflecting the lipophilicity of the molecule, volatility, the concentrations of the specialty and the high quantities handled.

Of 43 cytotoxics analysed, 3 active principles were retained. For each cytotoxic, a tracer was selected for its similar physical and chemical characteristics and its lower toxicity (the reference being the lethal dose, LD 50 in the mouse).

This analysis enabled us to select tracer active principles less toxic than the cytotoxics thus facilitating the implement simulations of cross contamination according to the various processes involved. The analytic method will be chosen to enable evidencing traces in the order of the µg.