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

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 sur...

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Main Authors: Maria Francisca Portilha-Cunha, Sara Ramos, Adrián M. T. Silva, Pedro Norton, Arminda Alves, Mónica S. F. Santos
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/14/8/754
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author Maria Francisca Portilha-Cunha
Sara Ramos
Adrián M. T. Silva
Pedro Norton
Arminda Alves
Mónica S. F. Santos
author_facet Maria Francisca Portilha-Cunha
Sara Ramos
Adrián M. T. Silva
Pedro Norton
Arminda Alves
Mónica S. F. Santos
author_sort Maria Francisca Portilha-Cunha
collection DOAJ
description 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 (R<sup>2</sup> > 0.997, IDLs < 4.0 pg/cm<sup>2</sup>, 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<sup>2</sup> (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<sup>2</sup>, except for three samples. The widespread presence of cyclophosphamide evinces the necessity to review implemented procedures.
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spelling doaj.art-85d73bf393684ee7a4d108dd7d1773962023-11-22T09:11:18ZengMDPI AGPharmaceuticals1424-82472021-07-0114875410.3390/ph14080754An Improved LC–MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace SurfacesMaria Francisca Portilha-Cunha0Sara Ramos1Adrián M. T. Silva2Pedro Norton3Arminda Alves4Mónica S. F. Santos5LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465 Porto, PortugalInstituto de Saúde Pública, Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, PortugalLaboratory of Separation and Reaction Engineering—Laboratory of Catalysis and Materials (LSRE–LCM), Faculty of Engineering, University of Porto, 4200-465 Porto, PortugalDepartamento de Saúde Ocupacional, Centro Hospitalar Universitário São João, 4200-319 Porto, PortugalLEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465 Porto, PortugalLEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465 Porto, PortugalCytostatics 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 (R<sup>2</sup> > 0.997, IDLs < 4.0 pg/cm<sup>2</sup>, 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<sup>2</sup> (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<sup>2</sup>, except for three samples. The widespread presence of cyclophosphamide evinces the necessity to review implemented procedures.https://www.mdpi.com/1424-8247/14/8/754antineoplastic drugscytotoxic drugsoccupational exposurehealthcare workerssurface contaminationenvironmental contamination
spellingShingle Maria Francisca Portilha-Cunha
Sara Ramos
Adrián M. T. Silva
Pedro Norton
Arminda Alves
Mónica S. F. Santos
An Improved LC–MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace Surfaces
Pharmaceuticals
antineoplastic drugs
cytotoxic drugs
occupational exposure
healthcare workers
surface contamination
environmental contamination
title An Improved LC–MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace Surfaces
title_full An Improved LC–MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace Surfaces
title_fullStr An Improved LC–MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace Surfaces
title_full_unstemmed An Improved LC–MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace Surfaces
title_short An Improved LC–MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace Surfaces
title_sort improved lc ms ms method for the analysis of thirteen cytostatics on workplace surfaces
topic antineoplastic drugs
cytotoxic drugs
occupational exposure
healthcare workers
surface contamination
environmental contamination
url https://www.mdpi.com/1424-8247/14/8/754
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