Troubleshooting in Normal-Phase HPLC

One of the reasons why silica is not used by many analysts, even for separation problems that would best be solved with this stationary phase, are the decades-old reports of the kind  

It can be assumed that new columns are more prone to such problems than used ones in the latter, the most active adsorption centers will be blocked with contaminations from preceding injections. 

Solvents with low boiling point, such as pentane or diethyl ether, are less convenient. Usually, it is no problem to find substitutes with higher boiling point, namely hexane or methyl tert-butyl ether in these cases. If a low-boiling eluent needs to be used, it is advisable to install a pressure restrictor at the detector outlet This can be a Teflon tube of length 10 m and inner diameter 0.25 mm. 

In order to avoid problems with water contamination, it is best to use a dedicated HPLC instrument for normal-phase separations. If the same instrument is used for both reversed-phase and normal-phase separations, it will be necessary to rinse it exhaustively with tetrahydrofuran or isopropanol before the new eluent is pumped through. When the instrument is prepared for a normal-phase separation with a high proportion of a nonpolar solvent (i.e., with a low proportion of the 

Although the adventure of chromatography began over 100 years ago with normal-phase separations, this mode is underestimated today and is used less frequently than it deserves. It is an elegant technique for a large number of analytes that are soluble in non-aqueous solvents. 

---