Introduction The occurrence of toxic drug residues is a hot topic concerning emerging environmental contaminants. The occupational exposure to antineoplastic drugs could be severe for health-care personnel and general public attending potentially polluted areas (such as oncology departments and pharmacies of hospitals) because of high therapeutic concentrations. In addition, also urinary elimination by patients represents a source of contamination. Monitoring of drug residues is necessary to guarantee occupational safety and absence of pollution. As a consequence of the great reactivity it could be difficult to record measurable levels of antineoplastic drugs. The aim of this work is to artificially produce degradation compounds similar to those formed in metabolic/environmental pathways by adopting a photocatalytic process and to identify them in indoor environments. Methods Heterogeneous photocatalysis experiments were performed under simulated solar light adopting TiO2 as photocatalyst. Solar light simulation was obtained using a 1500 W xenon lamp, in a device equipped with a 360 nm cut-off filter, for 24 hours at room temperature. LC-MS analysis were accomplished on a LTQ-Orbitrap instrument, with an electrospray interface. Chromatographic separation were achieved on C18 reversed phase columns. Degradation products identification has been performed acquiring MSn spectra at 100,000 resolution, with internal standards, in order to have elemental composition confirmation. Under these conditions experimental uncertainity was < 5 mmass units. Photodegradation model was applied to cyclophosphamide and mitomycin. Studied substances and degradants were quantified in environmental samples. Preliminary data We chose cyclophosphamide and mitomycin, due to popular use of these drugs. Liquid chromatography appears the best technique for direct analysis of these samples (neither derivatization nor complex extraction procedure for polar compounds), together with an high resolution MSn detection that empowers diagnostic identification and metabolites characterization. In antineoplastic drugs photocatalytic degradation, many oxidative degradants were formed using the simulation model, beside some hydrolysis and molecule breakdown sub-products. Main degradation products induced by photocalysis were hydroxyl- (on aromatic ring and aliphatic chain) and de-methyl derivatives. High resolution MSn spectra were used to identify and confirm the proposed structures. Kinetics of formation of the main degradation products have been studied by LC-MS. An highly sensitive method has been developed to measure the degradation products in wipe samples that allows detection of parent drugs at the ng level. Finally a study to characterize the untargeted analytes is ongoing to resolve the mixture of degradation products.. Findings will be compared to the proposed degradation mechanisms. Novel aspects Identification and measurement of new drug-derived environmental contaminants and their photodegradation products in indoor environmental samples

Antineoplastic drugs as occupational contaminants: photocatalytic degradation of molecules of different stability

MEDANA, Claudio;CALZA, Paola;DAL BELLO, FEDERICA;BAIOCCHI, Claudio
2012

Abstract

Introduction The occurrence of toxic drug residues is a hot topic concerning emerging environmental contaminants. The occupational exposure to antineoplastic drugs could be severe for health-care personnel and general public attending potentially polluted areas (such as oncology departments and pharmacies of hospitals) because of high therapeutic concentrations. In addition, also urinary elimination by patients represents a source of contamination. Monitoring of drug residues is necessary to guarantee occupational safety and absence of pollution. As a consequence of the great reactivity it could be difficult to record measurable levels of antineoplastic drugs. The aim of this work is to artificially produce degradation compounds similar to those formed in metabolic/environmental pathways by adopting a photocatalytic process and to identify them in indoor environments. Methods Heterogeneous photocatalysis experiments were performed under simulated solar light adopting TiO2 as photocatalyst. Solar light simulation was obtained using a 1500 W xenon lamp, in a device equipped with a 360 nm cut-off filter, for 24 hours at room temperature. LC-MS analysis were accomplished on a LTQ-Orbitrap instrument, with an electrospray interface. Chromatographic separation were achieved on C18 reversed phase columns. Degradation products identification has been performed acquiring MSn spectra at 100,000 resolution, with internal standards, in order to have elemental composition confirmation. Under these conditions experimental uncertainity was < 5 mmass units. Photodegradation model was applied to cyclophosphamide and mitomycin. Studied substances and degradants were quantified in environmental samples. Preliminary data We chose cyclophosphamide and mitomycin, due to popular use of these drugs. Liquid chromatography appears the best technique for direct analysis of these samples (neither derivatization nor complex extraction procedure for polar compounds), together with an high resolution MSn detection that empowers diagnostic identification and metabolites characterization. In antineoplastic drugs photocatalytic degradation, many oxidative degradants were formed using the simulation model, beside some hydrolysis and molecule breakdown sub-products. Main degradation products induced by photocalysis were hydroxyl- (on aromatic ring and aliphatic chain) and de-methyl derivatives. High resolution MSn spectra were used to identify and confirm the proposed structures. Kinetics of formation of the main degradation products have been studied by LC-MS. An highly sensitive method has been developed to measure the degradation products in wipe samples that allows detection of parent drugs at the ng level. Finally a study to characterize the untargeted analytes is ongoing to resolve the mixture of degradation products.. Findings will be compared to the proposed degradation mechanisms. Novel aspects Identification and measurement of new drug-derived environmental contaminants and their photodegradation products in indoor environmental samples
60th ASMS conference on mass spectrometry
Vancouver, BC, Canada
21-24 may 20122
60th ASMS conference on mass spectrometry
ASMS
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http://asms.org
C. Medana; P. Calza; F. Dal Bello; C. Baiocchi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/125314
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