Reporting Total Impurities for HPLC

[4meljones]

When reporting individual impurities for HPLC (or USPLC) where the impurity is not detected, I would report as less than the limit of quanitation (LOQ) for that impurity. For example, if the LOQ for "Impurity A" is 0.03 %, but the result was lower than this or not detected, I would report Impurity A as "< 0.03 %".

What would be the correct procedure for reporting Total Impurities where no impurites are detected at or above their respective LOQs? The LOQ for each imputiy may be different.

Please advise.

Regards
Melissa

[LC_labrat]

Do you have a specification for total impurities? I've seen it typically reported as <X.X% with X.X being the specification value. ICHQ3B has a reporting threshold value of 0.05% or 0.1% based on the maximum dose for drug products, you can also use that in place of specification if needed.

[Nour]

Let's say your TDI is higher than 1g: reporting threshold would be 0.1%
Case 1 LOQ < impurity A < reporting threshold
impurity A : report the obtained value or just express the result as < Reporting threshold (RT)
Case 2 LOD < impurity A < LOQ
impurity A: < LOQ
Case 3 impurity A < LOD
impurity A: Not detected (ND)

if the impurity is unknown and lower than reporting threshold don't take it into account in your calculation.

Note that LOQ should be lower or equal to reporting threshold.

[Nour]

[quote="4meljones"]

What would be the correct procedure for reporting Total Impurities where no impurites are detected at or above their respective LOQs? The LOQ for each imputiy may be different.

Total impurities is the sum of all impurities that are higher than reporting threshold. If all impurities are lower than the reporting threshold the result will be expressed as follows:

Total impurities: < reporting threshold (0.1% or 0.05% or as specified in the monograph)

[4meljones]

To clarify, I already have a method for reporting individual impurities that are not detected above their LOQ. I am concerned with how to report Total Impurities when none of the individual impurities are detected above their corresponding LOQs.

I considered the suggestion to simply report as "less than (the total impurities specification %)", as someone suggested, but this style of reporting would not show (at a glance, e.g. from an auditor or stability expert) that the result is not just "below the specification", it is very very low.

Just like using thresholds for idividual impurities, the total impurities should be reported to reflect how low the result really is, not just repeating the specification.

Any additional thoughts?

Melissa

[HPLCaddict]

In this case I'd report total impurities as "below reporting threshold (BRT)" or simply "nq".

[LC_labrat]

You could also use the highest LOQ as the reporting threshold.