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Using SelexION to Increase Selectivity for the Accurate and Sensitive Quantitation of a Difficult Peptide Therapeutic

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SelexION® DMS Technology Drives Advancements in Challenging Large Molecule Bioanalysis

By the End of 2024, the peptide therapeutics market value is expected to reach US$46.6 billion1. However, peptide therapeutics present some of the toughest analytical challenges for bioanalytical quantification. Large molecule therapeutics often may not fragment well for MS/MS analysis and often the case upon digestion in a complex biologic matrix this leads to an even higher background and potential for interferences.

To keep up with the pace of developmental therapies, Novartis Pharmaceuticals, along with SCIEX application specialists, recently developed a validated method to quantify pasireotide, a therapeutic peptide used to treat Cushing’s disease, in human plasma samples. The complete article was published in Analytical Chemistry and highlights how SelexION Technology on a QTRAP system can be used to increase selectivity for the accurate and sensitive quantitation of the difficult peptide therapeutic. To summarize the article, pasireotide, a therapeutic cyclic peptide exhibits poor fragmentation efficiency for multiple reaction monitoring (MRM) detections. Therefore, to increase the overall sensitivity of the assay, a DMS multiple ion monitoring (MIM) approach was explored. This method, utilizing the SelexION DMS cell on a QTRAP 6500, overcomes the sensitivity challenge in the typical MRM method due to the poor fragmentation of the analyte. What is great about this is the Pasireotide Method was developed and validated for bioanalytical analysis in human plasma down to 0.01 ng/mL, approximately 5-fold better than an MRM based method without using DMS separation – talk about improvements!

Over the past few years, researchers have needed to overcome the challenges associated with peptide bioanalysis in order to keep up with market demands. One way to do this according to Evgueni Fedorov, Executive Director, R&D, BIOTRIAL Bioanalytical ServicesOne, is to increase separation power. This was demonstrated in his webinar with SCIEX, where he showed how SelexION DMS technology on a QTRAP system can be used to enhance the selectivity of another challenging large therapeutic peptide, exenatide.

The Take-Away

  • Regulated Bioanalysis of challenging large peptide analytes using DMS technology is now a reality. Learn more in the Analytical Chemistry publication, and by watching an on-demand webinar, for a few examples.
  • The Jet Injector SelexION+ DMS device with increased transmission efficiency, shorter ion residence times, and improved robustness, used with the QTRAP 6500+ system, can provide enhanced selectivity and sensitivity to ensure better data quality, even for challenging large molecule analytes.
  • SCIEX R&D continues to put a keen effort into advancing the SelexION DMS technology to bring it into routine bioanalysis use

References

  1. https://www.marketwatch.com/press-release/peptide-therapeutics-market-value-to-reach-us466-billion-by-the-end-of-2024-transparency-market-research-2017-12-15

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