New Intermediates of Dealkylation of [ 14C]Atrazine by Mouse Liver Microsomes

Abstract

The metabolism of 50 μ M [2,4,6- 14C]atrazine by liver microsomes from ICR strain mice produced metabolites not previously described which account for about 25% of total transformation products, plus 10-14% deethylatrazine and 13-15% deisopropylatrazine, based on the total radioactivity injected into an analytical high-pressure liquid chromatography (HPLC) system. The unknown metabolites were observed by HPLC of products from atrazine incubations with liver microsomes from both untreated mice and mice treated with phenobarbital. Two major unidentified peaks (Unknowns 1 and 2) were isolated and collected by HPLC and characterized by gas chromatography-electron-impact ionization-mass spectrometry. Unknown 1 was an unstable intermediate, likely a mixture of carbinolamines, that decomposed into deethylatrazine, and Unknown 2, a mixture of compounds unseparated by HPLC probably with N-vinyl substituents at the location of the N-isopropyl and N-ethyl groups of the atrazine molecule with M + at m/ z 213. While microsomal oxidation did produce a mixture of trace amounts of breakdown products of atrazine, the method was impractical for the initial goal of preparing pure dealkylated atrazine derivatives for environmental degradation studies.