Atazanavir (ATV) is an antiretroviral drug of the protease inhibitor class. 
Multiple adverse effects of ATV have been reported in clinical practice, such as 
jaundice, nausea, abdominal pain, and headache. The exact mechanisms of 
ATV-related adverse effects are unknown. It is generally accepted that a 
predominant pathway of drug-induced toxicity is through the generation of 
reactive metabolites. Our current study was designed to explore reactive 
metabolites of ATV. We used a metabolomic approach to profile ATV metabolism in 
mice and human liver microsomes. We identified 5 known and 13 novel ATV 
metabolites. Three potential reactive metabolites were detected and 
characterized for the first time: one aromatic aldehyde, one α-hydroxyaldehyde, 
and one hydrazine. These potential reactive metabolites were primarily generated 
by CYP3A. Our results provide a clue for studies on ATV-related adverse effects 
from the aspect of metabolic activation. Further studies are suggested to 
illustrate the impact of these potential reactive metabolites on ATV-related 
adverse effects.