Stationary phases with high-purity silica

What is the reason for the overwhelming acceptance of stationary phases based on high-purity silicas in the pharmaceutical industry The answer is simple superior peak shapes for analytes with basic functional groups, which has been a problem with older phases. The older, low-purity silicas contain metal ions buried in the matrix of the silica. These contaminants acidify the surface silanols, and the consequence is a strong and non-uniform interaction with basic analytes. This in turn results in tailing peaks, which is an impediment for accurate peak integration and peak resolution. Of course, adding appropriate additives, such as amine modifiers, to the mobile phase can solve these difficulties. But this is an unnecessary and undesired complication in methods development. Therefore, silicas that are free from this complication are much preferred. 

Another example is the purification of a p-lactam antibiotic, where process-scale reversed-phase separations began to be used around 1983 when suitable, high pressure process-scale equipment became available. A reversed-phase microparticulate (55—105 Jim particle size) Clg silica column, with a mobile phase of aqueous methanol having 0.1 M ammonium phosphate at pH 5.3, was able to fractionate out impurities not readily removed by liquid—liquid extraction (37). Optimization of the separation resulted in recovery of product at 93% purity and 95% yield. This type of separation differs markedly from protein purification in feed concentration ( 50 200 g/L for cefonicid vs 1 to 10 g/L for protein), molecular weight of impurities (<5000 compared to 10,000—100,000 for proteins), and throughputs ( l-2 mg/(g stationary phase-min) compared to 0.01—0.1 mg/(g-min) for proteins). 

Metal contamination of the matrix of the silica, especially by aluminum and iron, also increases the acidity of surface silanols and the heterogeneity of the surface. This is a problem that largely plagues older stationary phases, which are based on silicas derived from inorganic raw materials. Many modem silicas are manufactured from organic silanes. In such processes, a high purity of the silica can be maintained with the appropriate precautions. In turn, this results in reversed-phase bonded phases with superior behavior toward basic compounds, that is, without excessive retention or taOing. 

Acclaim HILIC-10 is similar to Acclaim Mixed-Mode WAX-1. This relatively new column is also based on high-purity spherical silica covalently modified with a proprietary hydrophilic layer. It is suited for use in a broad range of applications including the separation of hydrophilic drugs and their metabolites. Acclaim Mixed-Mode HILIC-1 is a stationary phase that combines both RP and HILIC properties. Unlike traditional RP or HILIC columns, this packing material features a long alkyl chain with a diol functionality at the terminal end. 

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