Chromatography Forum

Hi !!

I am validating an impurity test. Is there anyone knows the recovery limits for LOQ ?

Thanks ...

Lime

Dear Lime,

You must calculate the 95% confidence interval (if you decide to use the 95%) and then you must check if the 100% value lies inside the interval. This way you can accept your recovery values.
If you want the equation for 95%CI, please tell.

Salfar

Thank you Salfar but isn't that equation for recovery studies. I mean for higher concentrations than LOQ such as 80%-120% ?
That would be perfect if you can give 95% CI calculation method .

Lime

Lime

There really isn't one specific concrete rule. The general idea is that your LOQ should be "comfortably" below the ICH reporting threshold (or spec), because that is the lowest level at which you would report values.

One can take a statistical approach, but this is not necessarily required. Our SOP calls for calculating the confidence interval based on repeated injections at the ICH reporting limit (or the spec). Then demonstrate that the lower arm of the confidence interval does not extend past the halfway point between the ICH limit or spec and the LOQ that's been determined.

Hope that helps, but probably I've just confused the heck out of you.

Adam

Thanks Adam ,

The problem is, I've already determined LOQ value, however when it comes to validate it, I have no idea about the recovery limits. I prepeared 3 samples in LOQ conc. and study recovery but don't know how to evaluate the results.

lime

Well I suppose you could demonstrate that the ratio of peak height to noise is equal to or greater than 10. Or you could evaluate recovery but with a wider range than you would for an accuracy experiment: maybee +/- 15%.

An easier approach would be to prepare samples at the detection limit (which you can generally take as LOQ/3) and demonstrate that they are detected. Basically "yep - I can see 'em"

OK, thanks Adam

lime

Your asking at LOQ level what is the limit of recovery.

It is 70 to 130% because it is very low level.

As per ICH 85 to 115% for higher side.

Thanks
Madhu

is this limit from ICH ? Cos I couldn't find any there

lime

is this limit from ICH ? Cos I couldn't find any there

Neither could I, at least not in their guidelines for the Validation of Analytical Procedures..

They do state (guideline Q2A) that the quantitation limit is "the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy." inferring that we should demonstrate repeatability and recovery at that low level. In guideline Q2B however, they state that the LOQ should be "validated by the analysis of a suitable number of samples known to be near or prepared at the quantitation limit" which we interpret as being satisfied by a suitable RSD on 5 LOQ samples.

The FDA's recommendation (document CMC3) is that the LOQ is validated by "Analysis repeatability and injection repeatability data at the quantitation limit" presumably meaning a suitable RSD on separate occasions. I didn't see any mention of accuracy/recovery at the lower limits in the FDA's guideline.

I wonder if anybody can provide further clarification in this thread?..