Chromatography Forum

Hi Everyone

Sorry for posting the incorrect question in my previous post (The brain does not work so well after 11pm). See correction below.

I need some help in determining relative response factors (RRF). The impurities that I am looking at are not readily available, therefore I need to calculate RRF for future determination.

Slope of impurity = 25557908 (from linearity curve)
Concentration of impurity = 0.0015 mg/ml
Slope of API = 30545354 (from linearity curve)
Concentration of API = 0.0010 mg/ml

Question ?

- How do I calculate RRF
- How do I use it to determine the % impurity when the impurity is not weighed off.

Thanks in advance
Mike Carolus

Your RRF would be approx 0.8 (slope of Imp/API) i.e. if you calc your impurity as 0.10%, then your final result for that imp is 0.12%. In this example, I really don't think you need to correct for this impurity i.e. generally don't have to correct if RRF is within 0.8 to 1.2

gtma,

Is there reference for the 0.8 - 1.2 window that doesn't need correction? I used to work for a RO and saw several methods from different clients that gave RRF values for impurities approaching 1 (e.g. 0.95).

Thanks

Not exactly an answer to your question but should be of interest if you are working with this.
There was an article about this on the USP Pharmacopoeial Forum, regarding different interpretations of RRF. We had quite an issue and a scare at work when we thought we were using them incorrectly. any way in the end nothing was done wrong but now we distinguish between RRF (relative response factor) and CF (correction factor).
The former is the denominator to the impurity peak area and the latter is multiplied to the impurity area. Tomorrow I'll try to post you the reference from work, if you're interested.

Hi,

According to EP 2.2.46 RRFs have to be used, if relative responses are smaller 0.8 and greater 1.2.
There can be reasons to use also relative response factors 0.8-1.2, especially if a impurity should be validated with narrow recovery limits (85-115%).
Btw: what are the acceptance limits generally used for Recovery of impurities?
One SOP I read states 2-4 times the method precision, but even the author was uncertain, how to define the method precision (just six determinations give you an impression, the value however will change from day to day and according to Murphy's law in validation you will get a very good precision, narrowing the recovery aceptance limits.) The Horwitz value can be helpfull in some cases.

Thank you all for the suggestions. I managed to find the USP reference.

Thanks again