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.

Join our email list for pharma news from SCIEX: Request information (sciex.com)

ADC analytics FAQs: Answering the most common questions about ADC characterization

Antibody-drug conjugates (ADCs) have emerged as one of the fastest-growing classes of biotherapeutics, combining the targeting specificity of monoclonal antibodies with the potency of cytotoxic payloads. However, this unique architecture also introduces significant analytical complexity. From drug-to-antibody ratio (DAR) distributions and charge variants to conjugation sites and structural modifications, ADCs present multiple, interconnected sources of heterogeneity that must be understood to ensure product quality and performance.

Sterile but toxic: Cereulide detection in food matrices

In a recent webinar, Ming Gao, Ph.D., Senior Research Chemist at Mérieux NutriSciences, explored the growing challenge of cereulide contamination in food products and the analytical strategies needed to detect this heat-stable toxin at trace levels. The session examined how LC-MS/MS can help laboratories overcome the limitations of traditional microbiological screening and meet emerging regulatory requirements.

How SCIEX Now empowers mass spec users to work with more control, clarity and confidence

In this interview, Andy Wilcox, Senior Market Development Manager, Aftermarket and Software, speaks with Susanna Baqué, Senior Director of Global Customer Experience, about how SCIEX Now gives customers one connected digital workspace to manage instruments, reduce time spent searching for information, resolve issues faster and keep their laboratory running more efficiently and with greater confidence.

Posted by

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.

0 Comments