Importance of Relative Response Factor in Impurities Quantification

Impurities are the constituent in drug product which isn’t the drug substance or an excipient.

Quantification of impurities in drug substance and drug product is achieved by HPLC.

What is Response Factor (RF):

The ratio among the concentration of a composite and its equivalent analytical response.

What is Relative Response Factor (RRF):

As per U.S. Pharmacopoeia (USP) The Relative response factor, is that the ratio of the responses of equal amounts of the Impurities then the drug substance or it’s reference standard. Different compounds at the identical conc. gives the variable responses and hence have varied RF values.

Why Relative Response Factor (RRF):

As per the International conference on harmonization (ICH) guidelines the foremost main aim is to estimate the impurities accurately and consistently as per defined reporting threshold, identification threshold and quantification threshold.

Quantification of impurity by using external standards is an impeccable method but it’s impossible in any respect the time because of lack of sufficient amount of impurities. Impurity isolation and synthesis is a difficult task and even should confirm its purity, quality and integrity by doing the periodic assessment.

Conclusion

The relative response factor is convenient for the estimation of impurities when it’s difficult to synthesis, or having very unstable or in absence of its standard. Probable robustness study of RRF to be performed during method development or validation. Accurately established RRF are utilized within the strategy of study with the acceptable conditions.

References:

1. United States Pharmacopeia, <1225> Validation of Compendial Procedures,
2. ICH Q2(R1), Harmonised Tripartite Guideline Validation of Analytical Procedures: Text and Methodology
3. ICH, Q3A (R2) Impurities in New Drug Substances: Text and Methodology,
4. ICH, Q3B (R2) Impurities in New Drug Substances: Text and Methodology.