(edited by Ohlbe on 2018-05-23 11:03)
Posting: # 18800
From the "Guideline on bioanalytical method validation" (EMEA/CHMP/EWP/192217/2009 Rev. 1 Corr. 2**, 21 July 2011) in Topic "4.1.9 Stability" mentioned about the stability of stock and working solutions that ' It is not need to study the stability at each concentration level of working solutions and a bracketing approach can be used'.
Which concentration should be use for bracket study in this experiment? It is need to be at ULOQ and LLOQ concentration, or not?
Can use high and low QC concentration (HQC, LQC) for this experiment as same as the other stability evaluations (in matrix)?
Edit: category changed [Ohlbe]
Posting: # 18803
» Which concentration should be use for bracket study in this experiment? It is need to be at ULOQ and LLOQ concentration, or not?
» Can use high and low QC concentration (HQC, LQC) for this experiment as same as the other stability evaluations (in matrix)?
Well, a bracketing approach validates whatever is between the brackets... If you use HQC and LQC working solutions you will not validate the stability of the working solutions below LQC and above HQC. So I would definitely recommend to use LLOQ and ULOQ.
This may seem illogical compared with the stability in matrix, where LQC and HQC are used, not LLOQ and ULOQ. But there is no other choice: when you analyse LLOQ samples, part of your results will be BLQ. Same for ULOQ samples: part of the results will be above the ULOQ. You would need to extrapolate on both sides of the curve, with no information on the resulting precision and accuracy. Not something you want to do to generate pivotal information.
Posting: # 18819
Is it ok to evaluate working solution stability according to FDA guidance May 2018 at LQC and HQC level.
As they have spoken about stock solution stability which has to be done at LQC and HQC level. Does it apply for working solution stability?