Setting recovery limits in impurites-AOAC

Dear all,

first of all i hope you and your family are all safe,
we are trying to set acceptance criteria for the recovery and precision in validation of impurities. We would like these criteria to be supported from official guidelines (as much is possible) in case we would be asked from authorities.
As in the ICH there are no limits for that, we are focused on AOAC Appendix F: Guidelines for Standard Method Performance Requirements
and specially in table A5: Expected recovery as a function of analyte concentration.
The question is what is exactly the ‘‘analyte concentration’’

  1. the percentage of analyte with respect to the API in the sample mass?


  1. the percentage of analyte with respect to the sample mass?

these two interpretations would lead to different recovery limits.
For an example, lets say that our sample test is 1tablet or 1000mg (in 20ml diluent) and the strength of the API in the tablet is 100mg. The LOQ of the method supposed to be 0.1% (LOQ is always defined as percentage with respect to the API) and we would like to set the recovery limits in this level.
If we take the first interpretation then 0.1% it will mean mass fraction C:
0.1/100 = 0.001 and mean recovery limits: 95-105%

But, if we take the second interpretation things are different. So the 0.1% means 0.1mg of analyte in 100mg of API or 0.1mg of analyte in 1000mg of sample mass. Then the mass fraction is 0.1/1000 = 0.0001, so from table A5 the mean recovery limits are: 90-107% !!!

We believe that teh second interpretation is the correct as it is independent of the strength of the API and behaves as a general rule.
I would like to have your comments on that
I hope that i did not confuse everyone,

kind regards


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