Stated plainly: dimerisation · cagrilintide · 25 °C.
The empirical answer seems settled. The explanation does not.
If the honest answer is that nobody knows, I would rather hear that than a plausible story.
What is the causal chain, and where does it stop being established?
At 25 °C the question is which route is fastest, not whether dimerisation happens — and the routes do not share an activation energy, so their ranking changes with temperature. 25 °C is 20 kelvin above the 5 °C middle of a 2–8 °C refrigerator. The ten-degree rule of thumb — degradation rate roughly doubling per 10 K — makes that about 4 times the refrigerated rate, which is an order-of-magnitude statement and not a shelf life. That multiplier is an average over every route at once, which is exactly why it cannot tell you which one wins. Two chains join, usually through a disulfide, so the product is roughly twice the mass and shows up as a late peak — or as nothing, if it never comes off the column. So the way to answer it for your vial is to pick the method that sees dimerisation specifically and run it against a control held cold, rather than to infer a mechanism from a purity number that averages all of them.
Start with the sequence, because which pathways are available depends on which residues are present.
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.
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.
Metal-catalysed oxidation of methionine is documented across peptide and protein formulations and is why chelators appear in some formulations.
Nothing here is medical advice, and research-use compounds are not approved for human use.
Swirl, never shake. Aggregation is a handling problem more than a time problem.
Aggregated, published test results and vendor ratings built from submitted batches. Methodology stated, dataset browsable, no listing fees.
Browse resultsThe 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.
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.
Apparent loss in a dilute preparation is usually adsorption rather than degradation and is worth ruling out first.
A mass spectrum names the pathway. Plus one, plus sixteen, minus eighteen.
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.
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.
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.
Adsorption losses at low concentrations are quantified in formulation studies and are the reason carrier proteins are used in dilute preparations.
Sequence decides which pathways are even available. Check the residues.
edited 17 Jan 2026 by h_pergande — clarified the distinction between purity and content
Worth being precise here: this is answerable from the chemistry rather than from anecdote, which is unusual and welcome.
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.
The caveat is that none of these pathways can be seen by looking at a vial, and a clear solution can be substantially degraded.
Cold, dry, dark, still. Those four words cover most of the mitigation.
The part that matters: asparagine and glutamine are the deamidation risk, and methionine is the oxidation risk.
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.
Deamidation via the succinimide intermediate is well characterised, with sequence-dependent rates highest for asparagine-glycine motifs.
Sequence determines which pathways apply, so general statements are general.
At dilute concentrations, suspect adsorption before you suspect chemistry.
edited 19 Mar 2026 by seven_day_half — expanded the table to cover the lower concentration
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