Impurity level question in MD

[shadow]

Hi all,
While developing a method for impurities on a drug product with a reporting threshold of 0.05%, the LOQ of the impurities was established first and based on the least sensitive of the impurities the sample preparation concentration was determined so the LOQ of the impurity would be below 0.05%. let's assume the chromatographic method is set in place with no room to change. A new impurity came in and the LOQ of this impurity is above the reporting threshold. We have looked at other wavelengths but we are working at the maxima in this case, increasing sample concentration is not possible due to solubility problems and injecting more sample is not possible as we are at 100uL. This impurity is not observed during stability and it barely shows up during forced degradation experiments. It is a potential degradation product, should this be included in the validation protocol? I need suggestions please. Thank you

[Blazer]

Out of curiosity, which forced degradation experiment creates this impurity?

My feeling at first glance is that if it's not seen on stability and it's not significantly generated through the typical forced degradation pathways, you can probably eliminate it from your validation protocol. I'd want to think about it a bit more.

When you say "just showed up" what does that mean?

[Consumer Products Guy]

I was still trying to figure out if "MD" meant Maryland or medical doctor...

[KM-USA]

I was still trying to figure out if "MD" meant Maryland or medical doctor...

Method Development? We don't use that abbreviation here.

[shadow]

Blazer, thank you for the response. This impurity is observed (<2%) at 80C, acid and base after several hours) but not during stability.

My apologies, MD=method development, noted.

[gtma]

It's important to note but I probably wouldn't be too concern given the harsh conditions used unless you feel it's likely genotoxic.