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

改进的 LC-MS/MS 方法用于分析工作场所表面的十三种细胞抑制剂

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作者:Maria Francisca Portilha-Cunha, Sara Ramos, Adrián M T Silva, Pedro Norton, Arminda Alves, Mónica S F Santos

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 µL 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 (R2 > 0.997, IDLs < 4.0 pg/cm2, 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/cm2 (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/cm2, except for three samples. The widespread presence of cyclophosphamide evinces the necessity to review implemented procedures.

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