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) [C
4H
10NO]
+, the loss of
N-ethylethanolamina [C
4H
10NO]
+ and
N-methylethanolamina
[C
3H
8NO]
+, the loss of CH
2OH 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.
