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 biopharmaceutical development, sequence variants (SV) are considered an inherent risk of producing complex proteins in living systems. Sequence variants are unintended changes to the amino acid sequence of a biotherapeutic and can be caused by errors in transcription or translation in the host cell, or cell culture and process conditions. Detailed analysis of SVs is important in process and product development to ensure the drug’s safety and efficacy. Even low‑level sequence variants can have significant implications for product quality, safety, and efficacy, making their accurate detection and characterization a critical requirement across development, process optimization, and regulatory submission.
CE‑SDS remains a cornerstone assay for characterizing fragmentation, aggregation, and product‑related impurities in therapeutic proteins. UV detection has been the long‑standing standard. However, it frequently struggles with baseline noise, limited sensitivity for minor fragments, and subjective integration.
At SCIEX, innovation doesn’t stop at instruments; it extends to how you interact with your LC-MS/MS or CE systems every day. That’s why we’re excited to introduce the SCIEX Now spring 2026 improvements: a set of meaningful enhancements shaped directly by your feedback.
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