Long-term stability

[parveenqa]

how do we determine the time period for carrying out LT stability for bioanalytical method validation of a compound????

[krickos]

Hi

First I assume that you refer to stability of solutions ie Robustness and not the long time stability of the compund itself (stability programs).

Of course depending of type and analysis you could do it a bit differently and also a bit depending on how often you think the analysis is performed.

Basicly I would do like this:
Sample solution just study it for a 1-2 days ie short time, as a principle you are supposed to use freshly prepared sample solutions, the only reasons to study this is basicly:
- if you run an analysis over night and instrument stops for some reason and you wounder if you can restart and use the same vial/solution without doing a new solution.
-if there is a quick degradation of the sample and you have to dissolve your sample just prior to injecting

Longer term stability of standard solutions are more intresting especially if it is a common analysis. I typically would do 2 solutions, one for storing at room temperature and one for 4-8°C. Only in a few rare cases have we streched the study past 30days. The people doing the analysis will thank you if you spend some time on this.

I also recommend to try digging up physical properties data for the substance, it may give you a hint on what to expect. Some substances (organic) in solution breaks down when exposed to daylight even in a quite short time period. Now you are talking biomolecules which is a bit outside my area and there might be other considerations there.

[JGK]

Tricky subject this one.

I would assume that you are talking about the Sample stability (analyte in the biological matrix).

I would recommend that you design an experiment to cover the time period you would expect to retain samples in storage (this may cover intermediate time points if necessary). However, I would also spike additional samples to enable an extension of the experiment should it become necessary (this would avoid any repeat of the experiment if the initial time period is insufficient.

[parveenqa]

thankyou
if i had to do pharmacokinetic study for a drug in volunteers and that study would take around 14 days, then is it necessary first to validate sample stability in biomatrix for that much time period????

[JGK]

thankyou
if i had to do pharmacokinetic study for a drug in volunteers and that study would take around 14 days, then is it necessary first to validate sample stability in biomatrix for that much time period????

If that is the maximum time a sample would remain in storage before analysis then yes you should validate for that time period.

In fact, I would probably try to extend the stability in excess of this duration to allow for a "worst case scenario" (instrument failure requiring extended downtime to repair).

[parveenqa]

[thank you