Analytical method of "Assay" and "related compounds" in USP

[bluejeans1014]

The USP monograph specifies the different LC analytical methods (i.e. the mobile phase and the gradient elution are different) for "Assay" and related compounds" in drug substance. Why the LC analytical method between "assay" and "related compounds" in USP monograph is diffenence, even the API peak can be detected as using the method of "related compounds" ? Could I just use the "related compounds" method of drug substance to test the " Assay" and "related compounds" of drug product if USP monograph doesnot specify the drug product ? Thank you.

[Karen01]

The USP monograph specifies the different LC analytical methods (i.e. the mobile phase and the gradient elution are different) for "Assay" and related compounds" in drug substance. Why the LC analytical method between "assay" and "related compounds" in USP monograph is diffenence, even the API peak can be detected as using the method of "related compounds" ? Could I just use the "related compounds" method of drug substance to test the " Assay" and "related compounds" of drug product if USP monograph doesnot specify the drug product ? Thank you.

They certainly don't HAVE to be different chromatographically (column, mobile phase, gradient) if everything is separated. They MAY have to be different because of sensitivity/quantitation requirements.

It is not unusual to have to inject more sample (higher conc or more volume) to quantitate related substances or impurities, so much that the API is off scale or out of the linear range.

From a time/efficiency standpoint it should be noted, as assay method does not need to separate all the related substances from each other, only from the API. This means that Assay method can be isocratic and much faster. That can be important for doing thing like content uniformity where you need to assay a lot of samples.

I've had situations where i used single method for purity and potency (assay) and others where they were separate.

- Karen

[bluejeans1014]

Thank you.

[bluejeans1014]

Even if the analytical method of "Assay" is consistent with "related compounds", we could use one method to analyte the sample if USP monograph doesn't specify it. We still see the USP monograph that has different method between "Assay" and "Related compounds", even the peaks of related compounds can be detected as using "Assay method". Has anyone known about the "Assay" and "Related compouns" in USP monograph of Pantoprazole sodium drug substance? What reasons that USP uses different method between the "Assay" and Test 2 of "related compounds"? Thank you. PS: I have tested that all related compounds specified in the test 2 can be detected as using "Assay" method, and the linearity of API signal is good.

[Bruce Hamilton]

Your questions should be directed to the USP, as they control the monographs.
They have a www site with contact details.

If you are selling a product as USP grade you either have to follow the prescribed methods or fully validate alternate methods to a level that would satisfy client auditors. The latter is not a simple or cheap exercise, but viable if you are planning on performing the analysis frequently, such as in a production environment.