Cytotoxic Surface Contamination in a Chemotherapeutic Preparation Unit: Method Development

Objectives

The aim of this study is to develop and validate a method of sampling and dosing of cytotoxic drugs to evaluate environmental and personal exposure to these drugs and optimize our production currently made in two separate isolators limiting cross-contamination between cytotoxic drugs and antibodies.

Methods

Cytotoxic drugs (CD) tested were chosen according to their physico-chemical characteristics, frequency of preparation and amount prepared. Risk cartography of sampling is carried out including critical points. Sampling method is developed with a test molecule and further extended to chosen molecules.
HPLC-DAD dosing method is validated and recovery rates are calculated.

Results

Cytotoxic drugs selected are 5-Fluorouracil (5-FU), cyclophosphamide (CP) and paclitaxel (PTX). Three areas of sampling are determined: preparation (isolators, gloves, bags), flows (transfer airlocks, worktops, floor) and analytical control. The sampling technique is validated with a deposit of ciprofloxacin (CPX) wiped with Whatman® paper, a wetting and dilution solvent (NaOH 0,03M + ACN 10%). In these conditions, recovery rates are 87% for CPX, 98 % for 5-FU, 92% for CP and 64 % for PTX. Retention times are 5.0 min for 5-FU, 7.7 min for CP and 10.8 min for PTX. Linearity is established from 0.5 to 25 µg/ml for 5-FU, 5-220 µg/ml for CP and 2-100 µg/ml for PTX. Limits of quantification are 0.5, 5 and 2 µg/ml respectively for 5-FU, CP and PTX. Accuracy and reproducibility are demonstrated for each CD.

Discussion-Conclusion

This method allows to obtain satisfying recovery rates. Simultaneous dosage of these 3 CD is validated within defined concentrations areas. Quantification limits of our analytical method are comparable to those reported in literature. Surface contamination analysis could be performed with this method.