Abstract
Due to the genotoxic, carcinogenic and teratogenic mechanism of action, anticancer drugs are highly hazardous compounds. Their occurrence, fate, and effects in the environment have not been systematically studied as compared to other medicaments. Therefore, reliable data, including their stability and persistency, is required in order to assess it. Taking into account, that hydrolysis is one of the most important factors regarding stability of chemicals in water, the aim of our study was to investigate the hydrolytic stability of five commonly used anticancer drugs (ifosfamide, cyclophosphamide, 5-fluorouracil, imatinib, and methotrexate) and one metabolite (7-hydroxymethotrexate), as the systematized and coherent data available is limited. The hydrolysis studies have been prepared according to the OECD 111 procedure to obtain standardized and comparable results. The preliminary tests at pH 4, 7, and 9 and 50 °C show that only cyclophosphamide and ifosfamide are unstable, whereas the estimated t1/2 at 25 °C is >1 year for other investigated compounds. Moreover, much more detailed experiments were performed and indicate that at environmentally relevant temperatures, cyclophosphamide, and ifosfamide would be quite persistent in the terms of hydrolytic stability. Moreover, the preliminary investigation on the hydrolysis products was performed.
Highlights
Anticancer drugs belong to the group of pharmaceuticals whose presence in the environment has gain the scientific attention much later than other popular groups of medicaments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or antimicrobials
The working solutions of the analytes were prepared in specific buffers in concentration of 10 mg L−1 each. Even though such concentration is higher than it is found in the environment, if the hydrolysis process follows a pseudo-first-order reaction the half-lives are independent of concentration (OECD 2004)
Presented results show that most of the investigated cytostatic drugs as well as one metabolite were stable under the test conditions
Summary
Anticancer drugs belong to the group of pharmaceuticals whose presence in the environment has gain the scientific attention much later than other popular groups of medicaments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or antimicrobials. Due to their genotoxic, mutagenic, and teratogenic mechanism of action, they belong to highly hazardous compounds (Mišík et al 2014). The available data is quite diversified in the terms of the threat and risk they might pose On one hand, their concentrations in hospital effluents
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