Does liraglutide adsorb measurably to the vial wall at 2.5 mg/mL?

For reference: liraglutide · 2.5 mg/mL.

I would rather understand the derivation than memorise the outcome.

Two people I asked gave two answers that differ by a factor of ten, which is suggestive.

Can someone walk through the arithmetic step by step?

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.

Answer first: the degradation pathways worth knowing are hydrolysis, deamidation, oxidation, aggregation and adsorption, and each has a different trigger and a different mitigation.

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.

Degradation pathway by condition

Light exposure matters for tryptophan-containing sequences and for anything with a chromophore. Amber vials and a closed box are free mitigations.

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

Cold, dry, dark, still. Those four words cover most of the mitigation.

The short version: water enables most of it, oxygen enables oxidation, surfaces enable adsorption, and agitation enables aggregation.

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.

Aggregation is physical: peptides unfold at air-liquid interfaces and associate. Shaking maximises that interface, which is why swirling and shaking produce visibly different outcomes on the same vial.

Adsorption losses at low concentrations are quantified in formulation studies and are the reason carrier proteins are used in dilute preparations.

At dilute concentrations, suspect adsorption before you suspect chemistry.

edited 1 Apr 2026 by tare_weight — added a caveat about sampling

The underlying point is that this is answerable from the chemistry rather than from anecdote, which is unusual and welcome.

Adsorption onto glass and plastic is significant at low concentrations — micrograms per millilitre — and negligible at milligrams per millilitre. It is the usual explanation for an apparent loss in a dilute preparation.

In practice, freeze-thaw cycling drives aggregation through concentration at the ice interface and pH shifts as buffer components crystallise out at different rates. Each cycle costs something.

Sequence decides which pathways are even available. Check the residues.

More usefully, aggregation is a physical process and is the one most often caused by handling rather than by time.

Oxidation targets methionine, cysteine and tryptophan, adding sixteen daltons per oxygen. It is catalysed by trace metals and promoted by dissolved oxygen and by light.

Swirl, never shake. Aggregation is a handling problem more than a time problem.

The relevant point is that a mass shift of plus one dalton is deamidation and plus sixteen is oxidation, so degradation is often visible in a mass spectrum if anyone looks.

A mass spectrum resolves most of this: minus eighteen is dehydration or succinimide, plus one is deamidation, plus sixteen is oxidation, and an unchanged mass with a shifted retention time is an isomer.

A mass spectrum names the pathway. Plus one, plus sixteen, minus eighteen.