Characterizing GLP-1 Therapeutics: Analytical Challenges and Solutions

Meet the expert panel exploring the challenges involved in GLP-1 analysis in this LCGC International Peer Exchange®.

Nitish Sharma and Piotr Alvarez compare reversed-phase separations of small molecules vs. peptides, from pI value and hydrophobicity to impurity profiles.

The panel walks through confirming peptide identity–from HRMS and LC–MS/MS sequencing to amino acid analysis and D/L-isomer verification.

How can analysts resolve impurities that differ by a single mass unit? Experts discuss deamidation, racemization, HRMS, and 2D-LC for GLP-1 peptides.

Piotr Alvarez explains how his lab uses 2D-LC to enable MS compatibility with legacy methods and to confirm peak purity through orthogonal separation.

The panel cover protecting peptide recovery, from mobile-phase pH and diluent buffers to inert column hardware.

The panel discusses quantitative peptide analysis, including drug substance vs. drug product complexity, recovery, and methionine oxidation risk.

Panelists identify the parameters that make or break peptide method robustness and tech transfer, including temperature, flow rate, and dwell volume.

Piotr Alvarez explains how HILIC complements reversed-phase LC for GLP-1 peptides, and why the field is moving toward MS-friendly TFA alternatives.

The panel considers how AI and automation could reshape peptide method development, and why scientific judgment will remain essential.