Determination of Response factors of Impurities in Drugs by HPLC

Importance of Relative Response Factor in Impurities Quantification

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

Quantification of impurities in drug substances and drug products 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 than the drug substance or its reference standard. Different compounds at the identical concern. 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 the 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.

A precise response factor is resulting from the assessment of every compound by using the appropriate detector. RRF is determined by using the following equation:

Conclusion:

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 condition.

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.