Relative Response Factor.The relative response factor (RRF) can be used to

correct for differences in relative response between the related substances and

the drug substance. In the area percent and high–low method, the related sub-

stances are calculated against the response of the drug substance. In the external

standard calculation, the standard curve of drug substance is generally used in

the calculation. Since the related substances are calibrated by the response of the

drug substance, it is necessary to determine the relative response of the related

substance to that of the drug substance. After the linearity of the related sub-

stances and the drug substance are determined, one can calculate the relative

response factor by comparing the slope of the related substance to that of the

drug substance. If the relative response factor is significantly different from unity,

a correction factor may need to be used in the calculation. Otherwise, the reported

results will be grossly over- or underestimated (Figure 3.10).