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Does survodutide adsorb measurably to the vial wall at 2 mg/mL?

Asked 28 Nov 2025Modified 5 months agoViewed 13k times
13

Concretely: survodutide · 2 mg/mL.

Please show the division. I want to check my own against yours.

I would like the general form as well as the specific number, so I can apply it again.

How many significant figures are actually justified here?

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askedanouk_desmet16k3828 Nov 2025
Same question here after a warm delivery, so I am following this. – nils_karlberg 6 months ago
Worth saying whether the vial has been opened, because that starts a different clock. – Dr_Bram_Verhoeven 4 months ago
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5 Answers

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38

2 mg/mL is 2000 µg/mL — roughly 200 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 2 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.

Light exposure matters for tryptophan-containing sequences and for anything with a chromophore. Amber vials and a closed box are free mitigations.

Reported and extrapolated stability by condition

StateConditionUsable windowBasis
Lyophilised solid−20 °C, sealed, dry24–36 monthsSupplier guidance
Lyophilised solid2–8 °C, sealed12–24 monthsSupplier guidance
Lyophilised solid25 °C, sealed4–8 weeksExtrapolated (Arrhenius)
Lyophilised solid40 °C, sealed1–2 weeksExtrapolated
Solution, preserved2–8 °C28 daysUSP microbiological convention
Solution, preserved25 °C3–7 daysExtrapolated
Solution, unpreserved2–8 °C24 hoursUSP microbiological convention

Windows for the solid state are chemical; windows for solution are microbiological and usually shorter than the chemical limit.

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.

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answeredkwn_analytical147k35820 Jan 2026
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25

The underlying point is that this is answerable from the chemistry rather than from anecdote, which is unusual and welcome.

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.

On the detail: 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.

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.

Cold, dry, dark, still. Those four words cover most of the mitigation.

edited 12 Feb 2026 by marcus_thorbjorn — added the placebo-arm figures

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MT
answeredmarcus_thorbjorn9.4k1631 Jan 2026
18

On the detail: aggregation is a physical process and is the one most often caused by handling rather than by time.

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.

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.

Adsorption losses at low concentrations are quantified in formulation studies and are the reason carrier proteins are used in dilute preparations.

A mass spectrum names the pathway. Plus one, plus sixteen, minus eighteen.

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DV
answeredDr_Bram_Verhoeven84k24829 Dec 2025
7Worth adding that residual moisture predicts this better than any printed date. – ilaria_bertone 3 months ago
6The doubling-per-ten-degrees rule is the part I did not know and now use constantly. – seven_day_half 10 days ago
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14

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.

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.

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FC
answeredforty_two_c66k589 Jan 2026
11

Start 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.

Apparent loss in a dilute preparation is usually adsorption rather than degradation and is worth ruling out first.

Sequence decides which pathways are even available. Check the residues.

edited 14 Mar 2026 by bac_or_bust — added the method parameters

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answeredbac_or_bust33k1376 Mar 2026

Your answer

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.

Not medical advice. Research-use-only compounds are not approved for human use.