How much can I change HPLC method ( the content of organic solvent) pretending that it is the same pharmacopeial method? Where it is noted?

This is a *large* can of worms. For a thorough discussion see the article "System Suitability Tests in Regulatory Liquid and Gas Chromatographic Methods: Adjustments versus Modifications" on page 58 of the June, 1998 issue of Pharmaceutical Technology (Fuhrman, Dorsey, & Snyder are the authors). Basically, at this point there is no official position from the FDA on how much change constitutes "adjustment" (allowed) versus modification (requires revalidation).

You might also check out the thread "Changes in analytical method those require validation" in the archives here on Chromatography Forum.

Following is the proposal for USP (HPLC)methods:

Minor component: ±30% relative or ±2% absolute(whichever is greater)

Other components: NMT 10% absolute

No component can be omitted.

Can you point me to a page reference for that?

The limits are just the "proposals" made and are not included in USP.

OK, then I'll stand by my earlier statement (I'm the December 3 Anonymous, by the way), that it's still a gray area as far as the regulators are concerned.

The proposed guidelines in the article "System Suitability Tests in Regulatory Liquid and Gas Chromatographic Methods: Adjustments versus Modifications" on page 58 of the June, 1998 issue of Pharmaceutical Technology (Fuhrman, Dorsey, & Snyder are the authors) was seemingly adopted in the Pharmaceutical Forum. I believe it is PF 25-5. Rather large changes can be made without having to address revalidation issues. FDA has reviewed some of my work with changes made within the guidelines set in the above PF number and not had any issues with it. E-mail me for further details if needed.