MOXIDECTIN - CHARACTERIZATION OF CATTLE, SHEEP, AND RAT IN-VITRO AND IN-VIVO METABOLITES BY LIQUID-CHROMATOGRAPHY TANDEM MASS-SPECTROMETRY

Moxidectin, a macrocyclic lactone related to the milbemycins and avermectins, is a potent new endo- and ectoparasitic agent. The in vivo metabolism of moxidectin was studied in cattle, sheep, and rats with larger quantities of in vitro metabolites Prepared from liver microsomal incubations. Both in vitro and in vivo metabolites were characterized first by liquid chromatography/mass spectrometry to generate molecular weight information on the unknown metabolites. Liquid chromatography/tandem mass spectrometry was then employed to generate daughter ion spectra of the molecular species. These spectra characterized the structures of unknown metabolites and served as structural fingerprints for identification and correlation across species. The principal metabolites of moxidectin were determined to arise from monohydroxylation of the parent. Dihydroxylation and O-demethylation coupled with monohydroxylation were found to a lesser extent. Subtle differences in metabolism were observed between the species.