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

Abstract

Cytostatics are drugs used in cancer treatment, which pose serious risks to healthcare workers. Dermal absorption via surface contamination is the key exposure route; thus, rapid, reliable, and validated analytical methods for multicomponent detection are crucial to identify the exposure risk. A surface-wipe-sampling technique compatible with hospitals' safety requirements (gauze, 1 mL isopropanol) and a fast and simple extraction method (1 mL acetonitrile, 20 min ultrasonic bath, evaporation, reconstitution in 200 mu L acetonitrile), coupled with liquid chromatography-tandem mass spectrometry analysis, were developed. It allowed identification and quantification of 13 cytostatics on surfaces: cyclophosphamide, doxorubicin, etoposide, ifosfamide, paclitaxel, bicalutamide, capecitabine, cyproterone, flutamide, imatinib, megestrol, mycophenolate mofetil, prednisone. Good linearity, sensitivity, and precision were achieved (R-2 > 0.997, IDLs < 4.0 pg/cm(2), average CV 16%, respectively). Accuracy for four model surfaces (melamine-coated wood, phenolic compact, steel 304, steel 316) was acceptable (80 +/- 12%), except for capecitabine and doxorubicin. Global uncertainty is below 35% for concentrations above 100 pg/cm(2) (except for capecitabine and doxorubicin)-a guidance value for relevant contamination. Method application in a Portuguese university hospital (28 samples) identified the presence of seven cytostatics, at concentrations below 100 pg/cm(2), except for three samples. The widespread presence of cyclophosphamide evinces the necessity to review implemented procedures.