Three days at 37 °C is about 28 refrigerated days of equivalent exposure. 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. At 28 equivalent days a test is more likely to reassure you than to tell you something, which is a legitimate reason to run it and a poor reason to expect a finding. Either way, record the three days and the temperature now, while you still know them; an excursion you did not write down is an excursion you cannot interpret later.
The relevant physics is latent heat: a phase-change pack holds temperature only while it is changing phase, and once it has melted it is a warm mass.
A single phase-change pack in a thin-walled box holds below ten degrees for roughly one to two days at twenty-five degrees ambient, and under a day at thirty-five. On a nine-to-fourteen-day lane the material is at ambient for most of the journey whatever was packed with it.
Degradation pathway by condition
| Pathway | Dominant when | Detected by |
|---|
| Deamidation | Solution, neutral to alkaline pH | RP-HPLC, +1 Da on MS |
| Oxidation | Light, trace metals, peroxides | RP-HPLC, +16 Da on MS |
| Hydrolysis | Solution, extremes of pH | RP-HPLC, fragment masses |
| Aggregation | Agitation, interfaces, high concentration | SEC, visual haze; often invisible on RP-HPLC |
| Freeze-concentration damage | Freeze-thaw of buffered solution | SEC, loss of recovered content |
To be exact about it, arrhenius behaviour means the degradation rate roughly doubles per ten degrees. A week at thirty degrees is therefore a meaningful exposure for a solution and an immaterial one for a dry solid.
Phase-change pack hold time is a function of mass, latent heat and insulation, and published figures for small parcels are on the order of one to two days.
Solutions are a different question and deserve the worry the solids get.
5Aliquoting before the first freeze is the advice I wish I had read two years ago. – kwn_analytical 9 months ago add a comment