Metabolic Disposition of Chlorambucil in Rats

Abstract

1. The metabolic disposition of chlorambucil, 4-ρ-(di-2-chloroethyl)amino-phenylbutyric acid, was studied in the rat.

2. After oral administration of [¹⁴C]chlorambucil to rats, plasma, liver, and kidney showed the highest concentration of ¹⁴C. After intravenous administration, plasma and kidney were heavily labelled. Although plasma contained as much as 10% of the administered dose in the first few hours after administration, the level decreased to 1% by 24 h. Elimination of radioactivity was mainly through the kidney.

3. Ten metabolites were isolated and characterized by mass spectrometry. Most metabolites had undergone oxidation on the butyric acid side-chain to form phenylacetic acid and benzoic acid derivatives. Spontaneous degradation products of [¹⁴C]chlorambucil were analysed and compared with the metabolites.