During the manufacturing process of active pharmaceutical ingredients some unwanted substances are produced those are known as impurities. Some impurities are raised due to the degradation of actual drug.
Impurities in pharmaceutical drug substances and drug products are required to be analyzing for the quantity of the impurities. To determine the actual quantity of the impurity it is required to have impurity standard. In the absence of the impurity standard relative response factor (RRF) may be used to calculate the actual quantity of the impurity.
Q3B R2 of ICH Guidelines also says that if response factor is determined correctly, it can be used to measure the actual amount of impurity. Identification threshold, quantification threshold and reporting threshold are given by ICH and it is important to determine the impurities within these thresholds.
Related: ICH Guidelines for Pharmaceuticals
Relative Response Factor (RRF) is an alternate method for the determination of the quantity of the impurities present in pharmaceutical products and amount of the impurity can be calculated with the help of peak area of the components. Relative response factor is the ratio of the response of the impurity and the active pharmaceutical ingredient (API) under the identical chromatographic conditions (chromatographic column, temperature, mobile phase, flow rate etc). Relative response factor is determined by analyzing the impurity standard and API standard of equal concentration. Following formula is used to determine the response factor:
Response Factor (RF) = Peak Area
Concentration in mg/ml
Relative Response Factor (RRF) = Response Factor of impurity
Response Factor of API
Response factor for different products are different and should be determined for individual substance. Relative response factor determined on a particular detector cannot be used in the calculation of product determined on other detector because different detectors show the difference in the response of same compound.
Solutions of at least three different concentrations of standard and impurity are prepared and injected in HPLC. The slop of area and concentration of impurity and standard are calculated to determine the relative response factor.
Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
.moc.enilediugamrahp@ofni :liamE Need Help: Ask Question
Spread the Knowledge ⇩⇩⇩