Simultaneous determination of five cytotoxic drugs in surface wiped samples using liquid chromatography and tandem mass spectrometry for the control of environmental contamination in a comprehensive cancer centre

Abstract

ABSTRACT The most common strategy to assess the occupational exposure risk to hazardous drugs in cancer healthcare settings is by monitoring environmental contamination of work surfaces with cytotoxic drugs. Healthcare workers, especially pharmacy technicians and nursing, handle multiple hazardous drugs, so they really may be exposed to different cytotoxic drugs simultaneously. Therefore, simultaneous determination of several cytotoxic drugs provides a more accurate assessment of the real occupational exposure risk in healthcare settings. Our objective was to develop a method for surface wipe sampling and a quantification method for five cytotoxic drugs commonly used in chemotherapy treatments preparation: cyclophosphamide, 5-fluorouracil, epirubicin, gemcitabine and paclitaxel. Wiping procedure was performed using cellulose swabs moistened in a mixture solution containing acetonitrile, water, 2-propanol and methanol with 0.1% formic acid. The obtained extracts were simultaneously quantified by an LC-MS/MS method. Chromatographic separation was achieved using an Acquity UPLC® BEH C18 column by a gradient elution, and detection was carried out in multiple reaction monitoring mode with electrospray source operating in positive and negative ion mode. Wipe and extraction procedures developed were simple and easy to implement, being able to recover the cytotoxic target drugs from two type surfaces sampling, stainless steel surfaces and polyethylene bags surfaces. The analytical method was linear over the calibration range and the limits of quantification were 1 ng/mL for cyclophosphamide, gemcitabine and paclitaxel, 1.5 ng/mL for epirubicin and 5 ng/mL for 5-fluorouracil. Intra- and inter-day precision and accuracy for all drugs were always inferior to 15%. This work provides a suitable procedure to identify cytotoxic contamination on work surfaces, being a useful tool to monitor occupational exposure risk to hazardous drugs, as well as to evaluate the effectiveness of decontamination protocols applied and hazardous drug handling protocols in cancer healthcare settings.