Sir,
1.If a product has two drugs in combination, how do we go about for the quantification/identification of unknown impurities cropping up? As far as quantification is concerned, whose label claim (of the two drug)should be taken?
2. Is it necessary to take label claim in calculation in impurity calculation? if yes/no, why?
3. If you have single method for impurity for combined dosage form & there is unknown impurity in your sample, how will we identify whose impurity it is of the two drugs?

Forced degradation of pure actives or individual actives made up with placebo tablets (heat, oxidation, acid/base, etc. need to be considered). These will show which peaks come from which compound. You'll probably need to do LC-MS or some other technique to confirm what the degradates actually are (or work them out before hand using the structure of your compound). Once you know this you quantify the peaks against the active they come from (or get pure forms of the degradates and quantify against them directly). Impurities you will need to work out from using placebo injections and from the process used to manufacture your active compounds. Plus you may get impurities which are actually combination of the active and excipients.

Use the label claim in calculating degradates - the actual active content is going to be going down - that's why the degradates are forming!

For unknowns you first need to confirm that it is actually from your product - your original investigation into potential degradates and impurities will show what could form. Anything else is most likely going to be contamination, so you could only really do an area% of the total peak area.

If there are no known degradants in the drug products, how do you go about validating the method?