Does a GLP-1 receptor agonist adsorb measurably to the vial wall at 2.5 mg/mL?

Accepted answer

2.5 mg/mL is 2500 µg/mL — roughly 250 times the concentration at which surface adsorption is measurable. Losses to glass and plastic matter in the low microgram-per-millilitre range, where a monolayer on the wall is a real fraction of what is in solution. At 2.5 mg/mL that same monolayer is a rounding error. If you see an apparent loss at this concentration, suspect the dilution step or the assay before you suspect the wall.

Specifically, asparagine and glutamine are the deamidation risk, and methionine is the oxidation risk.

Deamidation converts asparagine or glutamine to the corresponding acid via a succinimide intermediate, adding one dalton. It is base-catalysed, accelerates above neutral pH and is the dominant aqueous pathway for many peptides.

Hydrolysis cleaves the backbone, most readily at aspartate-proline and aspartate-glycine sequences, and is acid-catalysed. In a dry solid it barely proceeds at all.

Aggregation at air-liquid interfaces is established from surface-tension and particle-count studies and is the basis for anti-agitation handling guidance.

The caveat is that none of these pathways can be seen by looking at a vial, and a clear solution can be substantially degraded.

At dilute concentrations, suspect adsorption before you suspect chemistry.