Kirsten Craven

An overview: LC-MS analysis of targeted protein degraders and their metabolites

Aug 14, 2024 | Blogs, Pharma, ZenoTOF 7600 system | 0 comments

Targeted protein degraders 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.

TPD analysis

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)

TPD metabolite identification

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:

Achieve more accurate structure assignments when identifying drug metabolites
Enhance sensitivity with Zeno trap technology
Simplify data acquisition and processing for metabolite identification

Metabolite identification workflow

What is electron-activated dissociation?

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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Kirsten Craven

Kirsten Craven is the Senior Global Marketing Manager for Pharma global strategic marketing at SCIEX. In this role, she manages strategic marketing for the pharmaceutical industry. Kirsten spent the first part of her career working in laboratories across multiple industries before moving into product management, and most recently pharma marketing.

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