impurity validation precision

[rgamage]

To test precision you need a sample with impurity. I don't have impurity to spike. How do I get my sample for precision test with reasonable impurity level and the same level for all precision work?

This is for quantitation of impurity content. Impurity content calculation is done against standard prepared using API RS.

[Mattias]

Do you mean precision of quantitation of impurity or main peak?

[krickos]

Hi

Would recommend that you check out the ICH Q2R1 guideline, chapter 1.2.2 and 4.2 gives some recommendations when you lack an impurity standard.

Also ICH Q3A can be helpful in this respect.

The way forward may be a bit different depending on:
are you working with a new or existing/generic drug substance? (other reference methods may be availeble)
do you lack one or all impurities?
at what level versus ICH Q3a identification limits is the impurity in question present in the drug substance?

For instance, in a new drug substance (max 2g daily dose)if the impurity is likely to be present around 0,10% in a commercial batch you are pretty much forced to isolate it and characterise the structure anyways.