The response factor is a term usually used in chromatography and spectroscopy useful for the calculation of quantitative responses in detectors that correlates to amounts of investigated analytes. The response factor is a correction factor allowing the calculation of the true value of an analyte's concentration when using internal standard calibration. The response factor represents differences in response between the analyte(s) and the internal standard for a particular detector. To find the accurate response factor or detector response factor (DRF), also called the detector response ratio, the response factor must be established experimentally for each analyte in each detector or detector system. Usually, the peak area is used in the calculation, but the peak height may be used as well.

Response Factor (RF)

The “Response Factor (F)” is the ratio between a signal produced by an analyte and the quantity of analyte that produces the signal.

Relative Detector Response Factor (RRF)

The relative detector response factor expresses the sensitivity of a detector relative to a standard substance. It is expressed on an equal mole, equal volume or equal mass or weight basis.

Ideally, and for easy computation, this ratio is unity. 
However, in real-world scenarios, this is often not the case.


•    Response factor

The response (e.g. peak area) of an analyte or drug substance or related substances per unit weight. Typically, the response factor of a drug substance (or any related substance) can be calculated by the following equation:

•    Response factor = RF = response (in response units) / concentration (in mg/mL)  

•    RF= peak area / concentration (mg/ml)

•    Relative response factor (RRF)

The ratio of the response factor of an individual related substance to that of a drug substance to correct for differences in the response of related substances and that of the drug substance. It can be determined using the following equation:

•    Relative response factor (RRF) = response factor of individual related substance/response factor of drug substance, or,     

•    RRF = RF impurity/RF Active Pharmaceutical Ingredients or API, or, 

•    RRF = slope impurity/slope Active Pharmaceutical Ingredients or API 

Notes to Correction Factor Calculation using Internal Standards

(Analyte peak area/ Analyte concentration) = F (Standard peak area / Standard concentration) 

•    The equation assumes linearity through the origin, no negative numbers, using an internal standard.

•    If a linearity curve is constructed for both the related substance and the drug substance by plotting the response versus the concentration, the relative response factor can also be determined by using the following equation.

•    Relative response factor = slope of related substance/slope of drug substance

•    The simplest calibration using the Response Factor is calculated by dividing the known amount of a component by the size of the peak it produces.

•    Response Factors can be determined by analyzing a single standard mixture containing all of the components to be calibrated.

The Response Factor approach makes two important assumptions:

•     The amount per size line passes through the origin.

•     The amount per size line is straight.

However, for a trustworthy calibration, both assumptions must be varified experimentally.

If the line is really straight and really does pass through the origin, then the response factor is valid.


http://www.fda.govRegulations and specific guidelines for the validation of analytical methods and procedures.

http://www.agilent.com/chem/pharmaqaqc: The Agilent Website for pharmaceutical QA/QC with monthly newsletter for regular updates. 

http://www.labcompliance.com: A website with regular updates including tutorials and many references

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