Capillary electrochromatographic testing of monolithic silica columns synthesized according to an experimental design approach

Monolithic silica capillary columns synthesized following a three‐level design were evaluated for the electrochromatographic separation of acidic and neutral compounds. The influences of four factors in the sol–gel synthesis, i.e. the concentrations of tetramethylorthosilicate (TMOS) and PEG in the starting mixture, the gelation temperature and the silanization modifying time, on the electrochromatographic performance of the resulting C18‐silica capillary monoliths were studied. The considered responses were retention factor, resolution, symmetry factor, column efficiency, electrokinetic porosity and the equivalent length of the monolith. The four factors were varied to change the pore structure and the surface coverage with octadecyl moieties, resulting in nine stationary phases. The retentive properties of the columns were initially characterized with alkylbenzenes. Next, the separation for acetylsalicylic acid (ASA) and its related compounds was optimized and used to evaluate the performance of the nine stationary phases considering six responses. A compromise between the different responses was found around higher concentrations of tetramethylorthosilicate and PEG with a lower gelation temperature and a modifying time of 2 h. Column efficiencies up to 96 000 plates/m and resolutions above 1.9 were obtained for the acetylsalicylic acid separation, with a sufficient EOF to yield rapid analysis, which showed improvements over the center‐point stationary phase.