Mobile phase composition adjustment

[Liza]

Hello all:


I'm new to the lab & would appreciate it if you could help me on the following...


Where can I find guidelines in the USP regarding mobile phase composition adjustment? (e.g. what is the max % organic that can be added to mobile phase for the adjustment of peak retention time)


Thanks in advance.

[ntruong]

There was a presentation by William B. Furman from US FDA about " how much can you change an official method before it isn't the official method any more." Based on his presentation and I remembered reading this guideline also from another source, you are allowed to adjust 10% for the ratio of solvent in mobile phase as long as the total composition is 100%. (e.g., 50:50 MeOH:H2O can be adjusted to 45:55 or 55:45).

[Liza]

Thanks, ntruong.


Does anybody have a link to a free copy of this presentation by William B. Furman?


Thanks.

[ntruong]

I know Mr. Furman has tried to propose these changes to the USP ofiicials to make it official back in 1997, you can contact him at
FURMANW@DDASTL.CDER.FDA.GOV
I hope he is still with the agency.
Good luck,

[Liza]

Ntruong:


Thanks again for the info. I will contact him.


I'm thinking that +/- 10% is a huge range for adjustment. For example, if the mobile phase composition is 90:10, it can be adjusted to 99:1 or 89:11 if we were to follow this guideline.


Any ideas?

[tom jupille]

To the best of my knowledge, there is no official USP guideline at this time. Three roughly comparable proposals have been "test-flown":

• R. Cox and G. Menon, PharmEuropa, 10 (1998) 58.
  
  W. B. Furman, J.G. Dorsey, and L.R. Snyder, Pharm. Technol., (June 1998) 58.
  
  Pharmacopeial Forum, 30(3) (May-June 2004) 1015-1017

The Pharmacopeial Forum reference is a draft of proposed allowable adjustment limits, but as far as I know, those limits have not been incorporated into the 2006 USP. I have no idea whether they will show up in 2007.

Bill Furman retired from the FDA in 1998. His participation in the Pharm Tech article was as a "private individual" (who just happened to share opinions of others within FDA ).

If I were managing a department, I would write an SOP defining the allowed adjustment levels in your lab, using the articles above as support. Otherwise, you have do justify adjustments on a case-by-case basis.

For proprietary (non-USP) methods, you should define the adjustment limits on the basis of robustness information gathered as part of validation.