GEN-MKT-18-7897-A
Aug 14, 2024 | Blogs, Pharma, ZenoTOF 7600 system | 0 comments
Read Time: 2 minutes
Targeted protein degraders (TPD) are a relatively new therapeutic modality that opens the potential to target disease-causing proteins. These disease-causing proteins have been highly challenging for traditional small-molecule therapeutics to treat, making TPDs an exciting new therapeutic modality.
We are still developing our knowledge about TPDs and their behavior and optimizing analytical protocols to characterize and monitor them within the drug development process.
TPDs are typically dosed at low levels which makes their analysis in complex biological matrices challenging. Bioanalytical scientists who work with TPD compounds are striving to develop sensitive assays that reliably detect nanomolar concentrations of these highly potent drug candidates.
Learn more here > Targeted protein degraders and PROTACs (sciex.com)
Metabolite identification (MetID) is a critical step in drug development due to its impact on drug efficacy and safety. LC-MS platforms provide good selectivity and sensitivity making it the preferred technique for MetID. Traditionally, LC-MS experiments have used collision-induced dissociation (CID) to fragment and identify the metabolites. With some metabolites, the fragment ions generated by CID do not always generate a conclusive result leading to alternative techniques being needed to meet the regulatory requirements. Deploying electron-activated dissociation (EAD) can help in these circumstances.
In this webinar, An approach to streamline and simplify the identification of crucial metabolites from targeted protein degraders, Ebru Selen explains how EAD can be used for MetID analysis, allowing scientists to:
Metabolite identification workflow
Electron-activated dissociation (EAD) is a fragmentation technique available on the ZenoTOF 7600 system that causes ions in an LC-MS/MS experiment to fragment in locations that differ from where they fragment with CID, providing additional information to scientists. For metabolite identification, this could mean confident localization of the site of metabolism, removing the need for further safety testing.
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In monoclonal antibody (mAb) development, assessment of purity and integrity of the protein in question is critical. CE‑SDS is the gold standard assay and is routinely run from analytical development through QC and lot release. It’s trusted because it consistently delivers quantitative, size‑based insight into purity and fragmentation, and it fits naturally into regulated environments.
In drug discovery and development, Metabolite Identification (Met ID) plays a critical role in understanding biotransformation pathways, ensuring safety, and meeting regulatory requirements. Advanced mass spectrometry techniques have revolutionized this process, particularly through electron-based fragmentation methods such as Electron Activated Dissociation (EAD) and Electron Transfer Dissociation (ETD). While both techniques leverage electron interactions to generate informative fragment ions, they differ significantly in mechanism, performance, and suitability for Met ID workflows.
In analytical laboratories, performance is not optional. Whether supporting regulated pharmaceutical workflows, high-throughput CRO operations, clinical reporting, or food and environmental testing, your mass spectrometry and capillary electrophoresis systems are critical to productivity, compliance, and scientific confidence.
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