Metabolism of aniline mustard [N,N-di-(2-Chloroethyl)-aniline]

The possible metabolic activation of the antineoplastic agent N,N-di-(2-chloroethyl) aniline (aniline mustard) is discussed. Conversion of aniline mustard into the glucuronide $\text{(p-}\text{di}\text{-2-}\text{chloroethylaminophenyl}\text{-β-}\text{d}\text{-glucopyranosid}\text{)}$uronic acid was mediated by a rat liver homogenate containing the appropriate cofactors. The glucuronide was a major metabolite in the serum and bile after administration of aniline mustard to rats and after isolation and purification it was identified as its methyl ester by mass spectrometry. The use of Amberlite XAD-2 resin facilitated the isolation from serum of the glucuronide and another metabolite, N-(2-chloroethyl)-4-hydroxyaniline. The implication of these findings for the clinical application of aniline mustard is discussed.