Chloropyridinyl neonicotinoid insecticides: Diverse molecular substituents contribute to facile metabolism in mice

AGRO 3

Kevin A. Ford, kevin_fd@berkeley.edu and John E. Casida, kevin_fd@berkeley.edu. Environmental Science, Policy and Management, University of California, Berkeley, 115 Wellman Hall, Berkeley, CA 94720
Imidacloprid (IMI), nitenpyram (NIT), thiacloprid (THI), and acetamiprid (ACE) have in common the 6-chloro-3-pyridinylmethyl group but differ in the nitroguanidine, nitromethylene or cyanoamidine substituent on an acyclic or cyclic moiety. They were administered ip to mice at 10-20 mg/kg for analysis of brain, liver, plasma, and urine by HPLC/DAD, LC/MSD, and LC/MS/MS. Each compound was partially cleaved leading to the same eight urinary chloropyridinylmethyl-derived metabolites and various fragments from the rest of the molecule. IMI gave nitrosoguanidine, aminoguanidine, guanidine, olefin, methyltriazinone, and hydroxy- and dihydroxyimidazole derivatives. NIT metabolism involved N-demethylation and conversion of the nitromethylene substituent to carboxylic acid and cyano derivatives. THI yielded olefin, descyano, descyano olefin, urea, and hydroxythiazolidine metabolites and a ring-opened and methylated THI sulfoxide. ACE formed N-desmethyl and acetamide derivatives plus chloropyridinylmethylamine and N-methylchloropyridinylmethylamine. Despite their common metabolites, these neonicotinoids differ greatly in their sites of metabolism and persistence in mice.