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Is there any published stability data for survodutide at room temperature?

Asked 20 Jul 2024Modified 21 months agoViewed 52k times
38

For reference: survodutide · room temperature.

The claim is plausible, which is exactly why I want to check it.

I am able to read a paper if someone points me at one.

Is there data behind this, or is it received wisdom?

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DW
askeddana_wexler11k1620 Jul 2024

5 Answers

Accepted answer first, then by votes
33

Accepted answer

room temperature is one of the two points formal stability programmes actually run, so this is the rare case where the literature is looking where you are. Accelerated work is conventionally run at 25 °C and 40 °C, with the refrigerated condition as the control. Room temperature is not a number, so take the pharmacopoeial 20–25 °C and its 22.5 °C midpoint: 17.5 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 — puts that at about 3.4 times the refrigerated rate. It is an order-of-magnitude statement about a rate, not a shelf life, and the top of the 20–25 °C band runs about 1.4 times faster than the bottom of it. Whatever you find, check what was measured before you use it: a paper reporting purity at room temperature has not measured content, and the two fail at different rates for different reasons.

Answering this needs the physical state, since a dry powder is protected from most of these and a solution is protected from none.

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

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.

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

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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answered · acceptedsinead_gaffney28k3724 Sept 2024
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11

Answer first: the degradation pathways worth knowing are hydrolysis, deamidation, oxidation, aggregation and adsorption, and each has a different trigger and a different mitigation.

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.

In practice, 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.

Sequence determines which pathways apply, so general statements are general.

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

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FF
answeredfibre_or_fragment13k385 Oct 2024
7

The relevant detail is that aggregation is a physical process and is the one most often caused by handling rather than by time.

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.

Deamidation via the succinimide intermediate is well characterised, with sequence-dependent rates highest for asparagine-glycine motifs.

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

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DV
answeredDr_Bram_Verhoeven84k2482 Sept 2024
Worth adding that residual moisture predicts this better than any printed date. – loss_on_drying 22 days ago
The desiccant point is under-appreciated and costs nothing to act on. – stopper_core 2 months ago
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5

Concretely, this is answerable from the chemistry rather than from anecdote, which is unusual and welcome.

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.

At dilute concentrations, suspect adsorption before you suspect chemistry.

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EV
answeredekaterina_volk21k2813 Sept 2024
8The doubling-per-ten-degrees rule is the part I did not know and now use constantly. – e_dziedzic 4 months ago
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4

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.

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.

Metal-catalysed oxidation of methionine is documented across peptide and protein formulations and is why chelators appear in some formulations.

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

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TA
answeredtri_gly_ala24k388 Nov 2024
3I would add a sentence about light, since tryptophan-containing sequences care. – v_ramaswamy 7 months ago
4This should be in the site help pages rather than buried in an answer. – orla_ferriter 9 months ago
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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.