Let your application define your system solution.
In HPLC, components of a mixture are carried through the stationary phase by the flow of a mobile phase and separation is based on differences in migration rates among the sample components. Therefore, the nature of your analytes defines not only the method but also the HPLC system.
Main characteristics of the analytes:
MOLECULAR WEIGHT defines the pore size of the stationary phase
SOLUBILITY defines the HPLC mode, chemistry of stationary phase and eluent.
CONCENTRATION AND MATRIX define the detection parameters and column dimensions.
The solubility of your analytes defines the HPLC mode. The elutropic series defines the solvent strength for the most often used chromatography modes normal phase and reversed phase.