What I am working with: dimerisation · a GLP-1 receptor agonist · 37 °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 37 °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. 37 °C is 32 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 9.2 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.
This is answerable from the chemistry rather than from anecdote, which is unusual and welcome.
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.
| State | Condition | Usable window | Basis |
|---|---|---|---|
| Lyophilised solid | −20 °C, sealed, dry | 24–36 months | Supplier guidance |
| Lyophilised solid | 2–8 °C, sealed | 12–24 months | Supplier guidance |
| Lyophilised solid | 25 °C, sealed | 4–8 weeks | Extrapolated (Arrhenius) |
| Lyophilised solid | 40 °C, sealed | 1–2 weeks | Extrapolated |
| Solution, preserved | 2–8 °C | 28 days | USP microbiological convention |
| Solution, preserved | 25 °C | 3–7 days | Extrapolated |
| Solution, unpreserved | 2–8 °C | 24 hours | USP microbiological convention |
Windows for the solid state are chemical; windows for solution are microbiological and usually shorter than the chemical limit.
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.
Nothing here is medical advice, and research-use compounds are not approved for human use.
At dilute concentrations, suspect adsorption before you suspect chemistry.
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Browse resultsAnswering this needs the physical state, since a dry powder is protected from most of these and a solution is protected from none.
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.
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.
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