Metabolism of iphosphamide (2-(2-chloroethylamino)-3-(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) and production of a toxic iphosphamide metabolite.

Iphosphamide [2 (2 chloroethylamino) 3 (2 chloroethyl)tetrahydro-2//-l ,3,2-oxazaphosphorine 2-oxide] is metabolized by mouse liver microsomes in the presence of reduced triphosphopyridine nucleotide and oxygen. When purified aldehyde oxidase is added, the initial metabolites do not appear in quantity; but a single, anionic product is present. After chemical methylation, the mass spectrum of the product of the aldehyde oxidase reaction is identical to that of 2-carbomethoxyethyl Ar,A^'-bis(2-chloroethyl)phos-