Development of an analytical method for the determination of anthracyclines in hospital effluents.
ABSTRACT Little is known about the fate of cytostatics after their elimination from humans into the environment. Being often very toxic compounds, their quantification in hospital effluents may be necessary to individualise the putative magnitude of pollution problems. We therefore developed a method for the determination of the very important group of anthracyclines (doxorubicin, epirubicin, and daunorubicin) in hospital effluents. Waste water samples were enriched by solid phase extraction (concentration factor 100), analysed by reversed-phase high performance liquid chromatography (RP-HPLC), and monitored by fluorescence detection. This method is reproducible and accurate within a range of 0.1-5 micro g l(-1) for all compounds (limits of quantification: 0.26-0.29 micro g l(-1) ; recoveries >80%). The applicability of the method was proven by chemical analysis of hospital sewage samples (range: 0.1-1.4 micro g l(-1) epirubicin and 0.1-0.5 micro g l(-1) doxorubicin). Obtained over a time period of one month, the results were in line with those calculated by an input-output model. These investigations show that the examined cytostatics are easily detectable and that the presented method is suitable to estimate the dimension of pharmaceutical contamination originating from hospital effluents.
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ABSTRACT: Concerns about cytostatic anticancer drugs in the environment are increasing, mainly due to the lack of knowledge about the fate and impact of these cytotoxic compounds in the water cycle. In this context, the present work investigated the occurrence of 13 cytostatics and 4 metabolites in wastewater samples from various wastewater treatment plants (WWTPs) and from a large hospital from Spain. The target compounds belong to five different classes according to the Anatomical Therapeutic Classification (ATC), namely, alkylating agents, antimetabolites, plant alkaloids and other natural products, cytotoxic antibiotics and related substances, and other antineoplastic agents. Some of them have been classified as carcinogens in humans by the International Agency for Research on Cancer (IARC). These compounds were determined by an automated on line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method. Results showed the presence of methotrexate (MET), ifosfamide (IF), cyclophosphamide (CP), irinotecan (IRI), doxorubicin (DOX), capecitabine (CAP), tamoxifen (TAM) and the metabolites endoxifen (OH-D-TAM), hydroxytamoxifen (OH-TAM) and hydroxypaclitaxel (OH-PAC) at levels ranging from 2ngL(-1) (for MET) to 180ngL(-1) (for TAM). Some of these compounds were found to be efficiently removed after wastewater treatment, e.g. MET, DOX and IRI, whereas other compounds, such as TAM, CP and IF remained largely unaltered. The behaviour of the target compounds during the common filtration step of the water samples was also investigated with the finding that some compounds are strongly adsorbed to nylon filters, while cellulose acetate appears as the best choice for the filter material. The aquatic environmental risk associated to the detected compounds was also assessed. To the best of the authors' knowledge, this is the first report of the presence of the metabolites OH-D-TAM and OH-TAM in the water cycle.Science of The Total Environment 08/2014; 497-498C:68-77. · 3.16 Impact Factor
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ABSTRACT: Cytotoxic, also known as antineoplastic, drugs remain an important weapon in the fight against cancer. This study considers the water quality implications for the Thames catchment (United Kingdom) arising from the routine discharge of these drugs after use, down the drain and into the river. The review focuses on 13 different cytotoxic drugs from the alkylating agent, antimetabolite, and anthracycline antibiotic families. A geographic-information-system-based water quality model was used in the present study. The model was informed by literature values on consumption, excretion, and fate data to predict raw drinking water concentrations at the River Thames abstraction points at Farmoor, near Oxford, and Walton, in West London. To discover the highest plausible values, upper boundary values for consumption and excretion together with lower removal values for sewage treatment were used. The raw drinking water cytotoxic drug maximum concentrations at Walton (the higher of the two) representative of mean and low flow conditions were predicted to be 11 and 20 ng/L for the five combined alkylating agents, 2 and 4 ng/L for the three combined antimetabolites, and 0.05 and 0.10 ng/L the for two combined anthracycline antibiotics, respectively. If they were to escape into tap water, then the highest predicted concentrations would still be a factor of between 25 and 40 below the current recommended daily doses of concern. Although the risks may be negligible for healthy adults, more concern may be associated with special subgroup populations, such as pregnant women, their fetuses, and breast-feeding infants, due to their developmental vulnerability.Environmental Toxicology and Chemistry 09/2009; 28(12):2733-43. · 2.62 Impact Factor
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ABSTRACT: A study on the fate of two antineoplastic drugs, methotrexate and doxorubicin, in the aquatic environment is presented. The investigation involved a study of their decomposition under dark experiments, homogeneous photolysis and heterogeneous photocatalysis using titanium dioxide, the identification of intermediate compounds, as well as the assessment of acute toxicity over time. The analysis were carried out using LC (ESI positive mode) coupled with LTQ-Orbitrap analyser; accurate mass-to-charge ratios of parent ions were reported with inaccuracy below 10mmu, which guarantee the correct assignment of their molecular formula in all cases, while their MS(2) and MS(3) spectra showed several structural-diagnostic ions that allowed to characterize the different transformation products and to discriminate the isobaric species. Fourteen and eight main species were identified subsequently to doxorubicin or methotrexate transformation. The major transformation processes for doxorubicin involved (poli)hydroxylation and/or oxidation of the molecule, or the detachment of the sugar moiety. Methotrexate transformation involved decarboxylation or the molecule cleavage. Acute toxicity measurements showed that not only the two drugs exhibit high toxicity, but also their initial transformation products are highly toxic.Journal of chromatography. A. 08/2014;