The specifics, since they change the answer: deamidation · semaglutide · 40 °C.
I understand the observation; what I do not understand is the mechanism behind it.
I have read the two review articles that come up first and both assert this without a citation to a primary source.
Can someone derive this rather than assert it?
At 40 °C it can show up as either, and which one depends entirely on whether the product still elutes under the main peak. Purity is a ratio of areas, so a degradant only costs purity if the method resolves it. Content is a mass against a standard, so a degradant costs content whenever the parent is consumed — resolved or not. Asn and Gln lose the amide through a succinimide intermediate, so the product is one dalton heavier and usually resolves as a shoulder on the main peak rather than as a peak of its own. That is why the two measurements are not interchangeable and why an unchanged purity figure after an excursion to 40 °C is weak evidence: the method may simply be integrating the degradant along with the parent and reporting the sum as one peak.
Answer first: the degradation pathways worth knowing are hydrolysis, deamidation, oxidation, aggregation and adsorption, and each has a different trigger and a different mitigation.
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.
The part that matters: light exposure matters for tryptophan-containing sequences and for anything with a chromophore. Amber vials and a closed box are free mitigations.
Deamidation via the succinimide intermediate is well characterised, with sequence-dependent rates highest for asparagine-glycine motifs.
At dilute concentrations, suspect adsorption before you suspect chemistry.
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