Chromatography Forum

A 2% RSD on 5 consecutive injections of a 100% STD is the typically cited way of demonstrating "suitability". Was this number of 2% arbitrary or does it have statistical foundation?
As far as I can surmise, the F-distribution (in Statistics) that controls for Type 1 error is set at 0.05 or 5% of the tail in a distribution.
What is the origin of the 2% RSD criterion?

What is the origin of the 2% RSD criterion?

"Because we can." HPLC is fairly comfortable at that level, so no one wants to rock the boat.

If we wanted to do a better job, we would recognize that the precision of a measurement needs to be better than the precision required for control of the process or product. For example, if you need to control the potency of a tablet within +/- 5%, you had better be able to measure to about +/- 2% (or better). There is a whole branch of statistical quality control called "gauge theory" that deals with this (most of which is beyond my skill level!), but one useful concept for estimating how precise a measurement must be is the Wheeler "discrimination ratio". Here's a slide from our "Validating HPLC Methods" course:



Of course, this begets the question "why did they decide that 4 was the minimum for the discrimination ratio?" (I don't know the answer to that one! ).

USP itself is not that consistent. I've noticed that USP allows %RSD of 4 for alcohol test USP <611> and we're most often under 1, maybe that number was from manual injections, but that is an internal standard GC procedure. For parachloroaniline assay in 20% chlorhexidine solution, USP allows a 5% RSD.

Well this certainly helped to clarify the origin (and dare I say "rationale") for the 2.0% RSD criterion. Thanks for the slide T.Jupille.
Also, I noted that several exceptions to this criterion are well-cited in the literature (e.g. USP)--thanks ConsumerProdGuy.

So, then I must out ouf necessity pose this question: Is the notion of a 2% RSD an assay-dependent criterion? Because evidently the alcohol assay "611" does relax this criterion to 5%. So is it safe to say that it is assay dependent AND that whatever value it is established to be then it better be Less than the variance in the product/process we are measuring?

So is it safe to say that it is assay dependent AND that whatever value it is established to be then it better be Less than the variance in the product/process we are measuring?

Yes, I would agree with that.