Accepted answer
four weeks is 28 days, which at 2–8 °C is on the order of 28 refrigerated days. 2–8 °C is the condition the rule of thumb is anchored to, so it is the baseline rather than a multiplier: everything else in this thread is quoted relative to it. In solution the routes that matter are hydrolysis of the backbone, deamidation at Asn, and physical association — the first two cost content, the third costs neither until it precipitates. Over 28 days at 2–8 °C you should expect all three to have moved, and a purity figure to have noticed only some of them. Reconstituted material has no certificate; the one in the box describes the powder.
This is answerable from the chemistry rather than from anecdote, which is unusual and welcome.
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 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.
Swirl, never shake. Aggregation is a handling problem more than a time problem.
edited 25 Jun 2026 by Dr_Bram_Verhoeven — updated for the 2026 guidance change