What is difference between RRF and CF in related substances

Hi everyone
Please help regarding RRF and CF

In quantitating a drug impurity, you may think you can simply compare its peak area to that of the main peak and use this same ratio to determine its concentration, when the concentration of the main peak is known. However, this would assume that the two compounds have identical UV absorption or area at the analysis wavelength. Because this may not be the case, a direct comparison done in this manner is invalid.

Instead, you would use a reference standard of the impurity itself for direct quantitative comparison.
Response Factor (RF) = Peak area / concentration

Calculate RF for both the main peak standard and the impurity standard. Then calculate RRF:
Relative Response Factor (RRF) = RF impurity peak / RF main peak

Apply this correction factor to your impurity calculations and a quantitative comparison can now be made using the peak areas of the main peak and the impurity.


Other way to elaborate:

Relative Response Factor (RRF) and its Calculation in HPLC Analysis:
Know about the relative response factor and its calculation in system suitability parameters in HPLC analysis of pharmaceutical substances and pharmaceutical products.
During the manufacturing process of active pharmaceutical ingredients, some unwanted substances are produced those are known as impurities.
Some impurities are raised due to the degradation of the actual drug.
Impurities in pharmaceutical drug substances and drug products are required to be analyzed for the quantity of the impurities. To determine the
actual quantity of the impurity it is required to have impurity standard. In the absence of the impurity standard relative response factor (RRF) may be
used to calculate the actual quantity of the impurity.
Q3B R2 of ICH Guidelines also says that if the response factor is determined correctly, it can be used to measure the actual amount of impurity.
Identification threshold, quantification threshold and reporting threshold are given by ICH and it is important to determine the impurities within these
Related: ICH Guidelines for Pharmaceuticals
Relative Response Factor (full form of RRF) is an alternate method for the determination of the quantity of the impurities present in pharmaceutical
products and amount of the impurity can be calculated with the help of peak area of the components.
Relative response factor is the ratio of the response of the impurity and the active pharmaceutical ingredient (API) under the identical
chromatographic conditions (chromatographic column, temperature, mobile phase, flow rate etc).
Relative response factor is determined by analyzing the impurity standard and API standard of equal concentration. The following formula is used to
determine the response factor:
Response Factor (RF) = Peak Area
Concentration in mg/ml
Relative Response Factor (RRF) = Response Factor of impurity
Response Factor of API
RF in chromatography for different products are different and should be determined for individual substance. Relative response factor determined on
a particular detector cannot be used in the calculation of product determined on another detector because different detectors show the difference in
the response of the same compound.
Solutions of at least three different concentrations of standard and impurity are prepared and injected in HPLC. The slop of area and concentration of
impurity and standard are calculated to determine the relative response factor.
Also see: Theoretical Plates and their Determination in HPLC Analy


can you explain how to calculate total impurity, individual impurity in finished product as well as API. Please explain through case study.