Accepted answer
sixteen weeks is 112 days and, on a weekly schedule, 16 stopper punctures out of one vial at 2 mg/mL. Set the chemical question aside for a moment, because the puncture count is the one with a convention attached: 112 days is 4 times the twenty-eight days conventionally allowed for a preserved multi-dose preparation once it has been entered. Chemically, 2 mg/mL is high enough that adsorption to the glass is a rounding error and low enough that it is not protecting you from anything. What 16 withdrawals do add is 16 opportunities to introduce air, 16 coring events on the same stopper, and a headspace that grows with every draw — none of which show up on a certificate and all of which are avoided by splitting into aliquots at reconstitution.
This is answerable from the chemistry rather than from anecdote, which is unusual and welcome.
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.
Concretely, 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.
Aggregation at air-liquid interfaces is established from surface-tension and particle-count studies and is the basis for anti-agitation handling guidance.
Swirl, never shake. Aggregation is a handling problem more than a time problem.
edited 14 Aug 2026 by laminar_bench — added a caveat about sampling