Determination of urinary 2- and 3-dechloroethylated metabolites of ifosfamide by high-performance liquid chromatography

In vivo oxidation of chloroethyl side-chains on ifosfamide produces the toxin chloroacetaldehyde. Production of this labile metabolite can be indirectly quantitated by monitoring the excretion of the residual 2- and 3-dechloroethylated ifosfamide. Urinary ifosfamide and the two dechloroethylated metabolites were extracted into chloroform from alkalinized salt-saturated urine, followed by high-performance liquid chromatographic separation using an acetonitrile gradient on a reversed-phase column and ultraviolet detection at 190 nm. In five patients given 1.6 g/m² ifosfamide, 11–30% of the dose was excreted over 24 h as unchanged drug, 11–21% as 3-dechloroethylated and 3–10% as 2-dechloroethylated ifosfamide.