Why is it difficult to get reproducible retention times in normal phase chromatography?
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The reason for the variability in retention time in normal phase HPLC is the strong dependence of the retention on the content of highly polar mobile phase constituents, especially water.
Even if no water is added to the mobile phase on purpose, small quantities will always be dissolved even in very apolar solvents. Furthermore, bare silica is extremely hygroscopic, thus water will be adsorbed on the surface. Hence, the water content in a normal phase system can vary significantly and is rarely controlled. The equilibration of a normal phase column, especially when dealing with bare silica, can still take hours. That being said, polar modified stationary phases, such as cyano, diol or amino, are generally much less prone to variations in the water content of the mobile phase and can be equilibrated faster.