The Relative Response Factor (RRF) is an analytical measure used in chromatographic processes to monitor impurities/degradants in drug substances and drug products. RRF is utilized to compensate for the disparity in detector response of contaminants vs. analyte peak. It is established using the slope approach with a linear range of solutions.
Different pharmacopoeias use the word RRF differently. According to the United States Pharmacopoeia (USP), the relative response factor is the ratio of the responses of equal amounts of impurities to the drug substance. USP abbreviates RRF as Correction factor, Response factor, or Relative response factor.
According to the European Pharmacopoeia (Ph.Eur), the relative detector response factor, also known as the response factor, expresses a detector's sensitivity for a specific substance in comparison to a standard substance. The correction factor is the inverse of the response factor.
According to the British Pharmacopoeia (BP), the Response Factor is a relative phrase that refers to the response of equal weights of one drug to that of another under the test conditions stated. BP refers to RRF as the response factor. Establishment of RRF is required to avoid stability difficulties with standards, to minimize the cost of preparation of impurity standards, and to reduce maintenance of impurity standards, due to the absence of donation of impurity standards and difficulty in synthesis and isolation of impurity standards for convenience and time saving.
Relative Response Factor (RRF) is employed at many phases, including Phase 1 to Phase 4 investigations, drug purity testing, mass balance tests, limit tests, and stability indicating procedures. This value is crucial for quantitative or limit impurity tests because appropriate reference standards are not always accessible. The RRF parameter is sensitive to experimental settings; hence, its value varies when the chromatographic conditions change. While establishing the RRF, one should adhere to the exact procedure criteria without deviating from the original.
Parameters that influence RRF are change in column (same stationary phase from different column manufacturers), change in column particle size, changes in detector wavelengths, changes in detector, change in solvent grade, change in buffer concentration, and change in column temperature.
RRF Calculation
Formula = [Slope of Impurity (Known Impurity)/Slope of Active]