The Role of Relative Response Factor in Related Substances Method Development

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Relative Response Factor (RRF) is an analytical parameter used in chromatographic procedures to control impurities/degradants in drug substance and drug product. RRF is used to correct the difference in detector response of impurities with analyte peak. RRF is established by slope method with linear range of solutions. Different Pharmacopoeias refer the term RRF differently.

As per United States Pharmacopoeia (USP) The Relative response factor, is the ratio of the responses of equal amounts of the Impurities and the drug substance1. USP refers RRF as Correction factor or Response factor or Relative response factor.

As per European Pharmacopoeia (Ph.Eur) The Relative detector response factor, commonly referred as Response Factor, expresses the sensitivity of a detector for a given substance relative to a standard substance. The correction factor is reciprocal of the response factor2. Ph.Eur refers RRF as Correction factor or Response factor.

As per British Pharmacopoeia (BP) The Response Factor is a relative term, being the response of equal weights of one substance relative to that of another in the conditions described in the test3. BP refers RRF as Response factor.

Establishment of RRF is required to avoid the stability issues with standards, to reduce the cost on preparation of Impurity Standards, to reduce Maintenance of Impurity Standards, due to the lack of donation of Impurity Standards, difficulty in synthesis and isolation of Impurity Standards, for convenience and time saving. Relative Response factor (RRF) is used in different stages: Phase 1 to Phase 4 studies, in drug purity tests, Mass balance tests, in limit tests, In stability indicating methods etc.