Degradation and toxicity of mitoxantrone and chlorambucil in water

Abstract

The combination of liquid chromatography coupled to mass spectrometry (LC–MS) and acute toxicity studies with Daphnia magna was used to elucidate the water stability of the cytostatic compounds, mitoxantrone and chlorambucil, and their transformation products (TPs). Both compounds were rapidly degraded in water with the subsequent formation of bioactive TPs. Mitoxantrone suffered a rapid change in its conformation with the formation of four toxic TPs, which were unaltered and stable in water along the 2-day studied period. LC–MS analyses were allowed to identify the conformational changes of mitoxantrone that included the loss of the two amino alcohols (N-ethylethanolamina) [C₄H₁₀NO]⁺, the loss of N-ethylethanolamina [C₄H₁₀NO]⁺ and N-methylethanolamina [C₃H₈NO]⁺, the loss of CH₂OH from the original molecule and the formation of mitoxantrone dicarboxilic acid. Chlorambucil was also rapidly degraded in water loosing a hydroxyl group and forming a bioactive TP that further degraded within the following 12 h. The degradation of chlorambucil was also related to an exponential loss of toxic activity towards D. magna survival. The present results indicate that LC–MS methods should target TPs since field concentrations of these compounds measured in water may not reflect their toxicity.