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.
- Journal of Chromatography B: Biomedical Sciences and Applications. 01/1996; 683(2):133-134.
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ABSTRACT: Cytostatic anticancer drugs are an increasingly important issue in the environmental debate, mainly due to the lack of knowledge about the fate of these toxic substances. Over the last decades, 5-fluorouracil (5-FU) has been one of the most frequently used antineoplastic agents and may, therefore, be regarded as one of the pilot substances for environmental contamination. As a prerequisite for these investigations, a method for the determination of 5-FU in hospital effluents has been developed. Waste water samples were enriched by solid-phase extraction on ENV(+) columns (concentration factor 500) and analysed by capillary electrophoresis using a buffer containing 80% 160 mM sodium borate buffer (pH 9.5) and 20% acetonitrile (v/v). This method is applicable within the range 5-500 microg 5-FU L(-1). The standard curve (correlation coefficient >0.99) was linear with recovery rates from 80 to 96% and an accuracy from 9.0 to 20% (intra-assay standard deviation 0.7-8.9%; inter-assay standard deviation 2.2-9.5%). Based on the consumption of 5-FU in oncologic departments and the detection limit of 1.7 microg L(-1), this method covers the range necessary to evaluate 5-FU in hospital effluents. The applicability of the method was proven by chemical analysis of real hospital waste water samples. Obtained over a time period of 1 month (range 20-122 microg 5-FU L(-1)), the results were similar to those calculated by an input-output model. The presented method provides an analytical tool necessary to face the monitoring of environmental contamination problems.Analytical and Bioanalytical Chemistry 09/2004; 380(1):31-5. · 3.66 Impact Factor
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ABSTRACT: Doxorubicin (former generic name, adriamycin), a highly effective anticancer drug, produces cardiotoxicity, which limits its therapeutic potential. The mechanism of this cardiotoxicity has remained elusive. Our data suggest that this toxicity could involve doxorubicinol, the primary circulating metabolite of doxorubicin. Doxorubicinol was markedly more potent than doxorubicin at compromising both systolic and diastolic cardiac function. Similarly, doxorubicinol was much more potent than doxorubicin at inhibiting the calcium pump of sarcoplasmic reticulum [ATP phosphohydrolase (Ca2+-transporting), EC 126.96.36.199], the Na+/K+ pump of sarcolemma [ATP phosphohydrolase (Na+/K+-transporting), EC 188.8.131.52], and the F0F1 proton pump of mitochondria [ATP phosphohydrolase (H+-transporting, EC 184.108.40.206]. Our finding that this highly toxic metabolite was produced by cardiac tissue exposed to doxorubicin suggests that doxorubicinol could accumulate in the heart and contribute significantly to the chronic cumulative cardiotoxicity of doxorubicin therapy. Our observation that doxorubicin was more potent than doxorubicinol in inhibiting tumor cell growth in vitro suggests that the cardiotoxicity of doxorubicin is dissociable from its anticancer activity.Proceedings of the National Academy of Sciences 06/1988; 85(10):3585-9. · 9.74 Impact Factor