Stated plainly: dulaglutide · 5 mg/mL.
The units are where I keep going wrong, so please be explicit about them.
I have sanity-checked the order of magnitude and it seems right, which is not the same as being right.
Where is my error, and what is the correct working?
5 mg/mL is 5000 µg/mL — roughly 500 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 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.
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.
| 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.
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.
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.
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.
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.
The honest answer is that most reported "degradation" is adsorption and dilution error rather than chemistry.
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.
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.
Metal-catalysed oxidation of methionine is documented across peptide and protein formulations and is why chelators appear in some formulations.
The caveat is that none of these pathways can be seen by looking at a vial, and a clear solution can be substantially degraded.
Sequence decides which pathways are even available. Check the residues.
Put another way, this is answerable from the chemistry rather than from anecdote, which is unusual and welcome.
Light exposure matters for tryptophan-containing sequences and for anything with a chromophore. Amber vials and a closed box are free mitigations.
Sequence determines which pathways apply, so general statements are general.
Cold, dry, dark, still. Those four words cover most of the mitigation.
Start with the sequence, because which pathways are available depends on which residues are present.
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.
At dilute concentrations, suspect adsorption before you suspect chemistry.
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.