Normalization by a reference sample, also known as probabilistic quotient normalization (Dieterle F et al ), is a robust method to account for different dilution effects of biofluids. This method is based on the calculation of a most probable dilution factor (median) by looking at the distribution of the quotients of the amplitudes of a test spectrum by those of a reference spectrum.
A closely related method is normalization by a pooled reference sample, in which the reference sample is created computationally by using the mean values of the variables for a user specified reference group.