Orthogonal Fragmentation Mechanism Enables New Levels Of Metabolite Characterization

By Jason Causon, Kevin Bateman, and Rolf Kern, SCIEX and Christopher Kochansky, Merck

As  drug candidates progress through early to late stage drug discovery, more comprehensive metabolic studies are performed to characterize the site of metabolism, to inform researchers working to improve drug performance. MS/MS data is often required to fully characterize the metabolites, but this is difficult when the resulting metabolites become labile. Here, two orthogonal fragmentation techniques were compared to determine the in vitro metabolism of the drug darunavir. Using the ZenoTOF 7600 system and EAD fragmentation, the confident assignment and differentiation of O- and N-glucuronide conjugates was achieved.