Related Substances EP

[cdcl3]

I have the mandate to analyse the raw material cetirizine as per EP. However, I cannot obtain some of the impurities. Also, the STD preparation contains impurity A only, yet the EP specifications mention impurities A,B,C,D,E and F.

Where do I obtain these impurities, and how to quantitate all of them.

[Hemal]

As a manufacturer, you should have the impurity of your material and if you are the user of the material, the manufacturer should be able to provide you. It's required for characterisation of impurities.

Regards,

[adam]

Impurities are commonly quantified using the assumption of equivalent response factors (i.e. using the area percent method). So you don't necessarily need a standard for each impurity.

You are only required to identify (or characterize) the material, if it is seen above the ICH 'identification threshold'. Once you identify it, it is then a good idea to obtain some material and evaluate its response factor. Then you can continue to use the area percent method to quantitate it - but with a correction factor added to the method.

[ajaib5]

This is the common practice for determining the response factor for the impurities with respect to the API response. But the problem is the clear guidelines are not available on how to determine it and use it for the calculation.

There was an article in the pharmacoepail forum on the use of the response factor and in that the above problem was also highlighted. Even in the USP the use of response factor is mentioned differently for different products.

Regards

[Dan]

cdcl3,

As others have mentioned, you can quantitate the impurities relative to the drug substance using a relative response factor (RRF) that you determine experimentally if you have the impurities or you assume an RRF of 1.

If you do that, then you will not need reference standards of the impurities for quantitation. However, you would need them to find their retention times.

Please note that the above statements are generic for the impurity analysis of a drug substance.

What you need to do is look at your specific method. I looked up the EP monograph for cetirizine. This method has the impurities quantitated simply by a comparison of peak areas relative to the peak area of the drug substance in the "Reference solution (b)". All impurities (A, B, C, D, E and F as well as any unknown impurities) have a limit of not more than 0.1 percent). Again, the monograph method states that the quantitation is done by peak areas.

So you do not need reference materials for Impurities B, C, D, E and F. You do need Impurity A as there is a system suitability requirement for the resolution between Impurity A and the cetirizine. The EP monograph states that Impurity A is available as a certified reference standard.

One final comment, please be aware that those impurities listed in the EP monograph are only potential impurities, you may not find all of them in your particular batch of drug substance.

I hope this helps.
Regards,
Dan

[cdcl3]

Thanks all for your respond.