TABLE OF CONTENTS The IUPAC Compendium of Chemical Technology defines Normal Phase as an elution procedure in which the stationary phase is more polar than the mobile phase . In practice, the most widely used stationary phases for preparative HPLC are based on silica and the polarity of the underlying silyl ether and silanol provides the required hydrophilic surface. Amino and cyano bonded silica are also commonly used in normal phase mode though the latter also has some reversed phase properties. The predominant mechanism of interaction is hydrogen bonding. However, the silanol is mildly acidic so the silica surface will also have mild cation exchange properties.
Normal phase chromatography is commonly used to purify small organic molecules so the technique is regularly employed in the pharmaceutical and agrochemical industries. The progression from flash chromatography to preparative HPLC has been easy to comprehend for traditional organic chemists and this has probably driven the adoption of the technique for many pilot and plant scale separations. A concomitant transition from irregular particles to mechanically robust spherical stationary phase particles has also been fuelled by the increased demand. As stated earlier, irregular silica based particles are relatively fragile and, as such, are prone to degradation and generation of fines.
I have known the performance of irregular silica particles to improve with time and it has been postulated that this is due to erosion of the media to such an extent that the stationary phase has eventually become spherical.
