unspecified impurity treating

[stelef]

Dear all,

I am using an EP chromatographic method which appart from the known peaks gives one more as unspecified. It gives the structure but no RRT.
In our process there are 3 impurities more which can not be separated with this method. So, I developed one just to detect these new impurities, having as perpose to use 2 methods to analyse the sampe (one for EP's impurities and one for ours).But the unspecified impurity, previously mentioned, elutes at the same RT with the main peak. How should I treat to this unspecified impurity? Should I separate it from the main peak or since it is unspecified there is no need to mention anything about the specificity of the method as regards this impurity?

[krickos]

Hi

There are 2 comments I would like to make.

1. Any unspecified impurity in EP monographs for related substance testing by LC/GC. There is a general requirement, typically NMT 0,10% for any unspecified. This is included in recent updated monographs, but is also valid for non updated monographs as the 5.0th Edition of Ph Eur. In that edition examples are given in chapter 5.10 how to interpret this new rule also related to an update of general monograph 2032 (partly harmonisation with ICH Q3A).

so you can not overlook the unspecified impurity.

2. Appearantly the Ph Eur method is not suiteble for the intended purpose ie your process/product. Instead of running 2 methods I would recommend that you develop a method that resolves all impurities of intrest and submit that one to the authorities as the Ph Eur method is not fit for purpose. Sure it is a change but can not see an issue with regulators as the Ph Eur method obviously do not owrk for your product.

[stelef]

Hi!

thank you for the reply!
As regards the unspecified impurity it is checked with EP method. The only reason that I injected this and the other EP known impurities in in house method was to check the specificity of the latter. In our lab it is decided to use 2 methods since there are 11 impurities as summary and it is difficult to separate them with one method. But as I wrote this impurity (when checking specificity) elutes at the same RT as main peak. If it was a known peak I think than it will be problem for sure, but since it is unspecified? What should I do?

[krickos]

Ok
Perhaps I misunderstood you.

If you check impurity A-E + any unspecified with one method and impurity F-z + any unspecified with another method, it makes more sense, ie all impurities specified or not are determinded.

Coelution of impurities with main peak in either method can be handled by using external standards rather than internal normalisation (area %)

Hope thismade more sense

[stelef]

Thank you! This is helpful! In addition, with the second method (in house) I check only the known extra impurities, all unknown and unspecified are checked with EP's method.
An other issue is that the actual area of main peak won't change with the presence of this unspecified impurity, but I don't known if this is acceptable.