THE VERSATILITY OF PARALLEL HPLC FOR ENHANCED LC/MS/MS THE VERSATILITY OF PARALLEL HPLC FOR ENHANCED LC/MS/MS THROUGHPUT IN EARLY DRUG DISCOVERY

摘要

The use of multiplexing technology with targeted metabolite ID techniques shows great potential for increased productivity in early Discovery by providing project teams with both quantitative and qualitative compound information from single compound incubations (15(mu)l for HH and 25(mu)l for HLM) to further speed and guide synthetic efforts and optimization of pharmacokinetic parameters. In this study we confirmed the feasibility of our approach to rapid metabolite profiling. Numerous metabolites, that were consistent with literature findings, have been identified for all commercial compounds tested while utilizing the HH and/or HLM incubations used for HTS screening endeavors By injecting matrix only samples with several time points we were able to demonstrate, over time, the appearance of metabolites and disappearance of the initial substrate Both phase I and phase II metabolites were identified using either +/- ESI depending on the structural characteristics of the compound Enhanced product ion (EPI) spectra of putative metabolites were consistent with the fragmentation patterns/ions of the parent compound Several metabolites (single and bis-oxidations, multiple glucuronidations) were detected in an unknown sample and confirmed using this combined approach.