Reporting of Unknown Impurity at Very Low Percentage

[Terry]

Dear all,

I have a question in term of reporting unknown impurity in drug product as obtained via HPLC.

Let me say the specification for any single unknown impurity is NMT 0.05%, the area percentage of an unknown impurity is 0.00236%. In my opinion, there are several options to report the result: 1). 0.00%, 2). < 0.01%. Or I can set the minimum area threshold in my CDS (Ezchrome) higher to disregard this peak.

Which option would you choose? Any justification or regulatory reference?

Thanks in advance,

Terry

[prepcolumn]

Dear all,

I have a question in term of reporting unknown impurity in drug product as obtained via HPLC.

Let me say the specification for any single unknown impurity is NMT 0.05%, the area percentage of an unknown impurity is 0.00236%. In my opinion, there are several options to report the result: 1). 0.00%, 2). < 0.01%. Or I can set the minimum area threshold in my CDS (Ezchrome) higher to disregard this peak.

Which option would you choose? Any justification or regulatory reference?

Thanks in advance,

Terry

First of all 0.05% is a very low limit for a drug product. Anyway, if we turn back to your example. 1) 0.00% is not correct, because you can never report an impurity as 0. You have to write <Reporting threshold or <LOQ or <LOD or Not detected. 2) To report as < 0.01%, you have to be sure that this limit is over your LOQ limit.

[LC_labrat]

If the impurity result is below LOQ than set your minimum area at or near LOQ and disregard the peak. Your method validation determines you cannot accurately quantitate below LOQ level.

[Terry]

Concur. The problem for unknown impurity is that it does not have a LOD or LOQ. I think I should report < 0.01% (lower reporting limit, to the same decimal place with specification limt)

[LC_labrat]

The LOQ is based on the active analyte.