An investigation into the formation of tebufenozide's toxic aromatic amine metabolites in human in vitro hepatic microsomes.

摘要: Tebufenozide is a nonsteroid ecdysone agonist that causes premature and incomplete molting in Lepidoptera. Studies conducted so far have shown the low toxicity of tebufenozide mammals, birds invertebrates. potential metabolites such as aromatic amines are known to induce methemoglobinemia disorder humans, most likely by formation N-hydroxy metabolites; therefore, aim this research investigate toxic derivatives pooled human hepatic microsomal fractions. Analyses high performance liquid chromatography equipped time-of-flight detector (HPLC/TOF) indicated hydroxylated metabolite (exact mass=369; retention time: 6.65min) two de-dimethylethyl masses=313; times: 5.76 6.22min). Hydroxylated resulted from hydroxylation at either 3 or 5 position dimethylbenzoic acid moiety form 3-hydroxymethyl-5-methylbenzoic 1-(1,1-dimethylethyl)-2-(4-ethylbenzoyl) 3-methyl-5-hydroxymethylbenzoic 1-(1,1-dimethylethyl)-2-(4-ethylbenzoyl), respectively. The de-dimethylethyl-tebufenozide were 3,5-dimethylbenzoic acid-2-(4-hydroxyethylbenzoyl) acid-2-(4-ethylbenzoyl) acid-2-(4-ethylbenzoyl). Generally rates increased with incubation time. rate was approximately 12 times higher than ethylbenzoyl moiety. does not appear produce amine vitro microsomes. This suggests fate humans process detoxification rather activation.