Improved GLP-1 Receptor Agonist Peptide Recovery Using a QuanRecovery™ With MaxPeak™ High Performance Surfaces (HPS) Collection Plate

Importance of the Topic

The analysis of glucagon-like peptide-1 (GLP-1) receptor agonist therapeutics is critical in metabolic disease research and clinical testing, particularly for type 2 diabetes and obesity. These peptides feature large molecular weights and hydrophobic fatty acid conjugates, which lead to significant non-specific binding (NSB) losses during sample preparation. Improvements in sample handling can enhance assay sensitivity, reproducibility, and reliability in drug development and quality control.

Study Objectives and Overview

This study assesses the effectiveness of the QuanRecovery™ with MaxPeak™ High Performance Surfaces (HPS) 700 µL Collection Plate in minimizing NSB of common GLP-1 peptide drugs—semaglutide, exenatide, liraglutide, and tirzepatide—during LC-MS analysis. Comparative recovery rates against standard polypropylene plates are presented for 1 and 10 ng/mL peptide mixtures.

Methodology and Instrumentation

Peptide standards (10 µg/mL) were diluted to 1 and 10 ng/mL in 80:20:1 water/acetonitrile/formic acid. Samples were prepared in both QuanRecovery with MaxPeak HPS and polypropylene plates. A 4 min reversed-phase UPLC separation was conducted on an ACQUITY UPLC Peptide CSH C18 column at 65 °C using a gradient of aqueous and organic mobile phases containing 0.1% formic acid. Detection was performed by multiple reaction monitoring on a Xevo TQ-XS tandem quadrupole mass spectrometer. Injection volumes ranged from 5 to 10 µL.

Instrumentation Used

• ACQUITY UPLC I-Class PLUS System
• ACQUITY UPLC Peptide CSH C18 Column (130 Å, 1.7 µm, 2.1 × 50 mm)
• Xevo TQ-XS Tandem Quadrupole Mass Spectrometer
• QuanRecovery with MaxPeak HPS 700 µL Collection Plate

Key Results and Discussion

Use of the MaxPeak HPS plate demonstrated markedly higher MS responses for all four peptides at both concentration levels. Chromatograms showed reduced tailing and improved peak areas, indicating lower NSB. Recovery improvements were consistent across the panel, with the most hydrophobic peptides (those bearing fatty acid chains) benefiting significantly.

Benefits and Practical Applications

Integration of MaxPeak HPS collection plates in LC-MS workflows:

• Enhances recovery of large hydrophobic peptides
• Improves assay precision and sensitivity
• Reduces sample prep variability and peptide loss
• Simplifies method development for peptide therapeutics

Future Trends and Opportunities

Advances in specialized surface chemistries will further mitigate NSB for diverse biomolecules. Expansion of HPS technology to micro-flow and nano-flow formats could benefit proteomics and biopharmaceutical analysis. Automation-friendly formats may streamline high-throughput screening in drug discovery.

Conclusion

The QuanRecovery with MaxPeak HPS Collection Plate significantly reduces peptide loss from non-specific binding, leading to enhanced LC-MS performance for GLP-1 receptor agonist therapeutics. Adoption of this approach supports more robust bioanalytical assays and reliable data generation.