Development of an analytical method for the determination of anthracyclines in hospital effluents

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
Chemosphere (Impact Factor: 3.34). 11/2006; 65(8):1419-25. DOI: 10.1016/j.chemosphere.2006.03.069
Source: PubMed


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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    • "The analysis of organic pollutants in aqueous samples normally involves a previous filtration step of the samples to remove suspended particles. To date, different filtration materials have been indistinctly used in cytostatics research: cellulose acetate (Kovalova et al., 2009; Mahnik et al., 2006), nylon (Ferrando-Climent et al., 2013; Martin et al., 2011) or simply glass microfiber (Steger-Hartmann et al., 1996; Yin et al., 2010). However, to the authors' knowledge, the potential loss of the target compounds during the filtration step, eventually leading to underestimation of the final results, has not been investigated. "
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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.
    No preview · Article · Aug 2014 · Science of The Total Environment
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    • "Little information is available about the presence of this compound in hospital effluent and only Mahnik et al., in 2006, reported levels of this compound in the range 0.1 to 1.4 μg L −1 in a Vienna hospital [9], whereas it was not detected in a hospital effluent in Girona (Spain) [30]. The last compound, goserelin, was identified for the first time in one sample, at 0.35 μg L "
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    ABSTRACT: The occurrence of 26 commonly used cytostatic compounds in wastewaters was evaluated using an automated solid-phase extraction (SPE) method with liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Detection was optimized using Oasis HLB SPE cartridges at pH 2. Two hospital effluents and their two receiving wastewater treatment plants were sampled over five days. In hospital effluents, eight cytostatics were detected at levels up to 86.2 μg L(-1) for ifosfamide, 4.72 μg L(-1) for cyclophosphamide, and 0.73 μg L(-1) for irinotecan, the three most relevant compounds identified. Cyclophosphamide and megestrol acetate were found in wastewaters at concentrations up to 0.22 μg L(-1) for the latter. The predicted environmental concentrations (PEC) in sewage effluents of ifosfamide (2.4-4.3 ng L(-1)), capecitabine (11.5-14.2 ng L(-1)), and irinotecan (0.4-0.6 ng L(-1)), calculated from consumption data in each hospital, published excretion values for the target compounds, and wastewater elimination rates, were in agreement with experimental values.
    Full-text · Article · May 2014 · Analytical and Bioanalytical Chemistry
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    • "The environmental occurrence of pharmaceuticals has been widely reported and reviewed (Khetan and Collins, 2007). Concerning antimicrobial agents, several studies on their occurrence in wastewater and surface water have been published (Hirsch et al., 1999; Golet et al., 2002, 2003; Kolpin et al., 2002; Calamari et al., 2003; Giger et al., 2003; McArdell et al., 2003; Miao et al., 2004; Renew and Huang, 2004; Gobel et al., 2005, 2007; Joss et al., 2005; Lindberg et al., 2005, 2006; Nakata et al., 2005; Karthikeyan and Meyer, 2006; Mahnik et al., 2006; Batt et al., 2007; Gulkowska et al., 2008). "
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    ABSTRACT: Occurrence and behavior of fluoroquinolone antibacterial agents (FQs) were investigated in hospital wastewaters in Hanoi, Vietnam. Hospital wastewater in Hanoi is usually not treated and this untreated wastewater is directly discharged into one of the wastewater channels of the city and eventually reaches the ambient aquatic environment. The concentrations of the FQs, ciprofloxacin (CIP) and norfloxacin (NOR) in six hospital wastewaters ranged from 1.1 to 44 and from 0.9 to 17 micrgl(-1), respectively. Total FQ loads to the city sewage system varied from 0.3 to 14 g d(-1). Additionally, the mass flows of CIP and NOR were investigated in the aqueous compartment in a small wastewater treatment facility of one hospital. The results showed that the FQ removal from the wastewater stream was between 80 and 85%, probably due to sorption on sewage sludge. Simultaneously, the numbers of Escherichia coli (E. coli) were measured and their resistance against CIP and NOR was evaluated by determining the minimum inhibitory concentration. Biological treatment lead to a 100-fold reduction in the number of E. coli but still more than a thousand E. coli colonies per 100ml of wastewater effluent reached the receiving water. The highest resistance was found in E. coli strains of raw wastewater and the lowest in isolates of treated wastewater effluent. Thus, wastewater treatment is an efficient barrier to decrease the residual FQ levels and the number of resistant bacteria entering ambient waters. Due to the lack of municipal wastewater treatment plants, the onsite treatment of hospital wastewater before discharging into municipal sewers should be considered as a viable option and consequently implemented.
    Full-text · Article · Jul 2008 · Chemosphere
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