Hydrolytic stability of anticancer drugs and one metabolite in the aquatic environment

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 t 1/2 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.

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