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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The Echo® MS+ system is a novel platform for Acoustic Ejection Mass Spectrometry (AEMS) and combines the speed of acoustic sampling with the selectivity of mass spectrometry. This platform has been designed for high throughput analysis of small and large molecules. The technology combines Acoustic Droplet Ejection (ADE), an Open Port Interface (OPI) and could be coupled with the SCIEX Triple Quad 6500+ system or the ZenoTOF 7600 system.
The Echo® MS+ system comprises of an open-port interface (OPI) and acoustic droplet ejection (ADE) module which could be coupled with a mass spectrometer. The mass spectrometer could either be a SCIEX Triple Quad 6500+ system or the ZenoTOF 7600 system. This non-liquid chromatography based; high-throughput screening platform enables rapid analysis of compounds at speeds of up to 1 sample/second.
The ability to consistently achieve reproducible results on many complex samples across multiple days is critical to a routine clinical laboratory. Laboratories relying on analytical instrumentation require stability and robustness to perform a variety of screening and confirmatory assays with confidence. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the preferred analytical method in the clinical laboratory to reliably perform clinical testing as it provides best-in-class performance and reliability for the most challenging assays. LC-MS/MS offers the required levels of sensitivity and specificity for the detection and quantitation of molecules from complex biological samples, helping laboratories deliver highly accurate data for a variety of clinically relevant analytes across a wide range of assays.
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