Chromatography Forum

Hi Everyone,

This is less of a chromatography question and more of a regulatory one, but it is interesting nonetheless. I am working on a stability-indicating HPLC related substances assay for a pharmaceutical drug product. The API is actually a pro-drug, and it just so happens that the primary related substance (degradant actually) is the active form of the drug. The label claim of the drug product is listed as the active form of the API, rather than the pro-drug, i.e. XXmg of Compound A (pro-drug), equivalent to YYmg of Compound B (active form). So, the question is...how to report the potency determined by the HPLC method? Can the API assay (pro-drug) AND the degradant assay (active form of the API) be ADDED together to arrive at the label claim? Or, is the pro-drug quantitated by itself and then that potency is converted to the LC language? In the latter case, that makes the active form of the API a related substance with its own reporting criteria Has anyone run across anything similar to this? I have been asked this question (can the quantities be added together to calculate label claim), and I have not found a satisfactory answer anywhere. Thanks.

Hi there,

If the pro-drug is your drug substance (the rationale could be better stability, sustained effect or whatever) and that is what you’ve described in the manufacturing process (as I understand it) then you can’t just add the active form to the pro-drug and claim that the product is OK (i.e. a 100 % intact).
I can give you an example of something similar that might illustrate the situation (as I see it of course). It’s become very “fashionableâ€

I agree with Danko

Another example: The pro-drugs proctetive "functions" is related to the formulation, lets say a capsule, during "absorption of the body" the proctevtive groups are removed and the drug goes active. If the proctective groups are gone too early the drug may not work as well ie less potent.
I belive Bamuterol (pill/capsule) vs terbutaline (inhaled or i.v injection) is one such example.