Comman RS method for 15 API's

[kalidassa]

Hi to all actually i have developed a Residual solvent method which i have separated more than 20 solvents, Each and every API of ours having different solvents used in the process but i can cover more than 15 APIs in this list, Now what is doubt means

1) Can i give a general Method which standard preparation has all 20 solvents preparation for all the API's? Is there are issue to inject other solvents also in the standard, which not used in the process of the other API's?

2) My main aim is to validate this method and want to show the solution stability for this method and want to use same standard for all of our API's Residual solvent test.

[krickos]

Hi

First, sure many has used this approach but not as I know the way you want to do it. Usually they have a generic method for like Water and one for like DMF, where linearity precision etc has been established for each solvent individually. Then For each API the accuracy and stabilty of solution is verfied for each API with solvents of intrest, not all. This is the basic idea.

But what happens when you add 20 solvents at lets say 120% of their respective ICH Q3C limit into a standard compared to just those of intrest for a specific API? I am concerned that wou would get an additional matrix effect due to solvents interacting with each other, not just the API and sample solvent, while on trace levels this effect would be less.

Even from a single solvent aspect, headspace injections have in general a limited range/linerarity lest say up to 0,5-1,0%, there are exceptions like ethanol sure, but adding 20 solvents into one standard from 20to 120% of ICH Q3C limits with or without API present, well I would be happyly surprised if that works and the linearity curve do not break off.

[kalidassa]

Hi Mr.Krickos thanks for your point, actually while method development stage i have done all the studies like robustness, specificity, recovery and linearity study also, There is no problem in the method it works well for all of my API's, The least resolution i am getting in my method between a two pair of the solvents is 1.74, So there no problem in separation also, all limits i am following ICH limit only, My only doubt is how can i give method of analysis for each and every API's individually?, only those solvents used in the corresponding API or i can give all 20 solvents? if i can give means how can i give explanation for injecting other non specified solvents injected in the method.
Thank you for your advice in advance.

[Johnny Rod]

As long as your peaks of interest perform properly then I see no problem with having a mixed standard including peaks you don't use. In terms of writing methods, I would suggest you have one procedure describing how to prepare the standard, and all your API methods can refer to it. In each method you can detail the solvents of interest to be calculated, and the analyst can ignore the rest.