Method Development For Forced Degradation Of Small Molecule GLP-1 Agonist Orforglipron

Understanding how a small‑molecule GLP‑1 receptor agonist behaves under stress is essential for building confidence in its safety and long‑term stability. Walk through the development of an LC–MS impurity method for orforglipron, a non‑peptide, orally delivered GLP‑1 agonist currently under evaluation for obesity and type II diabetes. Using a systematic screening protocol, the method is constructed step‑by‑step—beginning with pH scouting to determine optimal retention, followed by column and solvent screening to uncover meaningful selectivity for impurities. The final method achieves strong resolution, sharp peak shape, and spectral purity that aligns with USP 621 guidelines. Analysts gain a clear view of orforglipron’s degradation pathways, helping ensure accurate impurity profiling and reliable quality‑control workflows.

Explore the full application note to see the chromatographic comparisons, optimization strategies, and final method performance data.