Metabolite Identification
For compounds exhibiting high metabolic clearance, it is of great value to follow up the metabolism by profiling and identifying the metabolites.Metabolite identification allows for
- Identification of unique and disproportionate metabolites
- Soft spot identification to direct the next round of syntheses
- Selection of appropriate pre-clinical tox models
- Facilitation of the identification of major isoforms of the metabolizing enzymes
- Understanding the fate of the drug and metabolites in clinical samples.
- Avoiding reactive metabolites
Assay MethodologyQuintara Discovery’s metabolite profiling and identification approach always starts with a well-designed compound incubation. Choosing the relevant in vitro systems, such as liver microsomes, S9, or hepatocytes, as well as in vivo systems, and executing with precision and rigor are prerequisites for a successful MetID effort. Metabolites generated are investigated by the Q Exactive™ Hybrid Quadrupole-Orbitrap LC/MS/MS system with full and data dependent scan. A customized data mining algorithm using Compound Discoverer software will be utilized to search and identify the metabolites. Detailed analysis will aim to identify the type of metabolism, the soft spot, and the chemical reaction that lead to the specific metabolite formation. Chemical structural elucidation of the metabolite can be achieved. |