The elution problem

This is then the general elution problem and there are several ways of dealing with it  

All the above alternatives aim to create a greater distance between the early peaks and to speed up the elution of the latter ones so that they become closer together. 

The elution problem does not occur in size-exclusion chromatography, which is one of its major advantages. Instead, elution of all components is guaranteed, the final ones coinciding with the void volume at the very latest. The only exception to this is in the case of adsorption effects, peaks being eluted later than Vq, but this can be prevented by a careful choice of stationary and mobile phases. 

Practical High-Performance Liquid Chromatography, Fifth edition Veronika R. Meyer 

Complex mixtures, i.e, those that contain 20 or more components, in most cases present separation problems. Under isocratic conditions (Fig. 18.1) the initial peaks are likely to be poorly resolved and the final peaks will probably be broad and flat and may be swamped by background noise. If a weaker solvent is used, the initial peaks show improved resolution but the final ones are not eluted at all. A stronger solvent compresses the early peaks together more, so that some components can no longer be distinguished. 

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