PeptideStack
5.2kquestions
20kanswers
220users

Is there any published stability data for liraglutide at 37 °C?

Asked 23 Jun 2026Modified 1 min agoViewed 2.9k times
10

The particulars: liraglutide · 37 °C.

Somebody stated this to me confidently and I would like to check it before repeating it.

I would accept a well-reasoned negative answer over a poorly sourced positive one.

What would count as evidence here, and does it exist?

peptide-stability
peptide-stability

The chemistry of peptide degradation: deamidation, oxidation, hydrolysis, aggregation and fibrillation, and how temperature, pH, ionic strength,…

908 questions
storage
storage

Storage conditions and their evidence base: minus twenty degrees for powder, refrigerated for solution, protection from light, and what the…

701 questions
clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

745 questions
liraglutide
liraglutide

A once-daily GLP-1 receptor agonist and the compound that established the class. Still relevant for its shorter half-life, its paediatric and…

235 questions
shareeditfollowflag
JE
askedjonas_ekstrom12k3823 Jun 2026
8Voting to keep this open — it is more specific than it first looks. – sian_llewellyn 3 months ago
add a comment

5 Answers

Sorted by votes
5

Probably not at 37 °C specifically, because that is not where stability programmes take their readings. Accelerated work is conventionally run at 25 °C and 40 °C, with the refrigerated condition as the control, so 37 °C sits between or beyond the published points and what you will find is bracketing rather than a measurement. 37 °C is 32 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 — makes that about 9.2 times the refrigerated rate, which is an order-of-magnitude statement and not a shelf life. Whatever you find, check what was measured before you use it: a paper reporting purity at 37 °C has not measured content, and the two fail at different rates for different reasons.

The short version: water enables most of it, oxygen enables oxidation, surfaces enable adsorption, and agitation enables aggregation.

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.

Degradation pathway by condition

PathwayDominant whenDetected by
DeamidationSolution, neutral to alkaline pHRP-HPLC, +1 Da on MS
OxidationLight, trace metals, peroxidesRP-HPLC, +16 Da on MS
HydrolysisSolution, extremes of pHRP-HPLC, fragment masses
AggregationAgitation, interfaces, high concentrationSEC, visual haze; often invisible on RP-HPLC
Freeze-concentration damageFreeze-thaw of buffered solutionSEC, loss of recovered content

To be exact about it, 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.

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

shareimprove this answerflag
DW
answereddeamidation_watch45k5825 Jun 2026
Thank you — this is the answer I was looking for. – Dr_Aoife_Brennan 2 months ago
The desiccant point is under-appreciated and costs nothing to act on. – jo_vandeberg 2 days ago
add a comment
Sponsored

Sigma-Aldrich - Certified Reference Materials

Analytical standards and reagents with traceable certificates. Every quantitative result you read inherits the accuracy of the standard behind it.

Shop standards
3

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

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.

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.

Nothing here is medical advice, and research-use compounds are not approved for human use.

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

shareimprove this answerflag
HP
answeredh_pergande71k15829 Jun 2026
4Worth adding that residual moisture predicts this better than any printed date. – kwn_analytical 4 months ago
add a comment
3

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

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 relevant detail is that 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.

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

shareimprove this answerflag
TA
answeredtess_amankwah22k273 Jul 2026
1

The honest answer is that most reported "degradation" is adsorption and dilution error rather than chemistry.

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.

The caveat is that none of these pathways can be seen by looking at a vial, and a clear solution can be substantially degraded.

Swirl, never shake. Aggregation is a handling problem more than a time problem.

shareimprove this answerflag
FR
answeredfib4_reader24k2712 Jul 2026
5The doubling-per-ten-degrees rule is the part I did not know and now use constantly. – ravenna_pace 4 months ago
add a comment
-1

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.

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.

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

At dilute concentrations, suspect adsorption before you suspect chemistry.

edited 22 Aug 2026 by Dr_Colm_Fitzhenry — reworded for clarity after a comment

shareimprove this answerflag
DF
answeredDr_Colm_Fitzhenry69k24728 Jul 2026
3Is there a reason to prefer minus eighty here, or is minus twenty genuinely enough? – Dr_Idris_Coulibaly 9 months ago
add a comment

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.