What I am working with: racemisation · orforglipron · room temperature.
I can predict the outcome but I cannot explain it, which means I will get the next case wrong.
I would like to know how confident the field actually is about this.
What is actually going on here, physically?
At room temperature 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. A stereocentre inverts. Identical mass, identical formula; only a chiral method or a peptide map with a chiral digestion sees it at all. That is why the two measurements are not interchangeable and why an unchanged purity figure after an excursion to room temperature is weak evidence: the method may simply be integrating the degradant along with the parent and reporting the sum as one peak.
The honest answer is that most reported "degradation" is adsorption and dilution error rather than chemistry.
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.
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.
Cold, dry, dark, still. Those four words cover most of the mitigation.
Aggregated, published test results and vendor ratings built from submitted batches. Methodology stated, dataset browsable, no listing fees.
Browse resultsStart with the sequence, because which pathways are available depends on which residues are present.
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.
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.
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.
The part that matters: 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 at air-liquid interfaces is established from surface-tension and particle-count studies and is the basis for anti-agitation handling guidance.
At dilute concentrations, suspect adsorption before you suspect chemistry.
edited 22 Jun 2026 by mz_4113 — reworded for clarity after a comment
The relevant detail is that this is answerable from the chemistry rather than from anecdote, which is unusual and welcome.
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.
Metal-catalysed oxidation of methionine is documented across peptide and protein formulations and is why chelators appear in some formulations.
A mass spectrum names the pathway. Plus one, plus sixteen, minus eighteen.
Asparagine and glutamine are the deamidation risk, and methionine is the oxidation risk.
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.
Adsorption losses at low concentrations are quantified in formulation studies and are the reason carrier proteins are used in dilute preparations.
Sequence determines which pathways apply, so general statements are general.
Sequence decides which pathways are even available. Check the residues.
Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.