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Five Key Advantages of the Thermo Scientific LC-MSn Solution for Ultra-Sensitive GLP-1 Quantitation

By 09.25.2025

Bioanalytical analysis using LC-MSn requires precise, accurate, and robust methods to confidently evaluate pharmacokinetics and toxicokinetics. This is particularly challenging for peptide-based biologics like glucagon-like peptide-1 (GLP-1), which have low circulating levels and require high sensitivity in complex biological matrices. The Thermo Scientific LC-MSn solution, featuring the Stellar mass spectrometer acquiring parallel reaction monitoring (PRM) MS2 and MS3, offers a new paradigm for routine bioanalysis of GLP-1, improving quantitative performance almost 16-fold compared to triple quadrupole mass spectrometers (QQQ MS).

GLP-1 image

Here are five key advantages of the Thermo Scientific LC-MSn solution for GLP-1 quantitation:

     1. Enhanced quantitative sensitivity

The Stellar mass spectrometer enables researchers to achieve quantitative sensitivity down to 0.03 ng/mL using both simple and complex sample preparation methods. This is a significant improvement over more common SRM/MRM methods, which often struggle to reach such low levels due to the limitations of MS2 quantitation of one product ion.

     2.  Parallel reaction monitoring (PRM) acquisition improved specificity with MS2 acquisition

The Stellar MS boosts measured signal-to-noise (S/N) ratios 3X at 0.05 pg/mL GLP-1 spiking levels through co-adding multiple MS2 product ion signal without adding noise. This enhances data quality and quantitative performance, allowing for more accurate and reliable results at LOD and LOQ levels.

     3. Reach next-level performance with SPS MS3 acquisition

Moving from PRM-based MS2 to MS3 increases the specificity and selectivity necessary for highly confident quantitation in complex biological matrices. Extending the MS3 performance using synchronous precursor selection (SPS) boosts the sensitivity needed to reach the same LOQ using more cost-effective sample preparation steps as MS2 acquisition with SPE. By co-isolating the three MS2 product ions prior to dissociation, more of the original precursor signal is measured at the MS3 level. Acquiring SPS MS3 using PRM also enables post-acquisition summation of multiple product ions realizing the same benefits as that described when using PRM-MS2.

     4. Simplified data acquisition with dynamic AGC

Dynamic automatic gain control (AGC) manages ion accumulation times to maintain a stable charge density across a range of GLP-1 expression levels. This ensures high data quality by improving ion statistics and maintaining robust and reproducible PRM acquisition. The user defines the targeted charge density, LC peak width, and number of data points, while AGC automatically adjusts ion fill times to ensure optimal data acquisition.

     5. Comprehensive workflow management with Chromeleon 7.4 CDS software

Chromeleon 7.4 software provides a unique software ecosystem managing the entire LC-MSn workflow, from data acquisition to customizable reporting. It handles unregulated and regulated data acquisition, data processing, and system suitability testing, ensuring compliance with stringent regulatory requirements. The software also facilitates collaboration and cross-study management with full traceability and verification throughout the data lifecycle.

Conclusion

The Thermo Scientific LC-MSn solution, featuring Chromeleon CDS software and the Stellar mass spectrometer, offers unparalleled sensitivity, specificity, and quantitative performance for GLP-1 quantitation. By leveraging advanced techniques such as PRM acquisition, SPS MS3 acquisition, and dynamic AGC, researchers can achieve reliable and accurate results with simplified sample preparation methods. Chromeleon 7.4 software further enhances the workflow by providing comprehensive data management and compliance capabilities that transitions from method creation to analytical quantitation.

For more information visit Chromeleon Software for Targeted Quantitation

For more information visit Stellar mass spectrometer

Visit us on LinkedIn: #GLP-1, #biologics, #PRM, #bioanalytical

Scott M. Peterman, PhD

Scott Peterman, Ph.D., is Senior Product Marketing Manager for Life Science Mass Spectrometry of the Chromatography and Mass Spectrometry Division of Thermo Fisher Scientific.