Does survodutide adsorb measurably to the vial wall at 20 mg/mL?

The case in front of me: survodutide · 20 mg/mL.

I want the working, not the result — I need to be able to redo it with different numbers.

I care about the precision as well as the value — I want to know how many figures are real.

Where is my error, and what is the correct working?

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

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.

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.

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

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

Asparagine and glutamine are the deamidation risk, and methionine is the oxidation risk.

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

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.

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

Concretely, 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.

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.

At dilute concentrations, suspect adsorption before you suspect chemistry.