Glucuronidation, an important metabolic process for the biotransformation of drugs into easily eliminable water-soluble detoxification products, can also lead to biologically active or toxic glucuronide conjugates. The present work describes a liquid chromatography-electrospray mass spectrometry (LC-ESI-MS) approach for the characterization of naproxen and O-6-desmethylnaproxen glucuronides. The method is fast and efficient and permitted to individuate alpha and beta isomers of both naproxen and O-6-desmethylnaproxen glucuronides. The procedure could be potentially extended to the characterization of other drug metabolites.