Bioanalytical liquid chromatography tandem mass spectrometry methods on underivatized silica columns with aqueous/organic mobile phases

This review article summarizes the recent progress on bioanalytical LC–MS/MS methods using underivatized silica columns and aqueous/organic mobile phases. Various types of polar analytes were extracted by using protein precipitation (PP), liquid/liquid extraction (LLE) or solid-phase extraction (SPE) and were then analyzed using LC–MS/MS on the silica columns. Use of silica columns and aqueous/organic mobile phases could significantly enhance LC–MS/MS method sensitivity, due to the high organic content in the mobile phase. Thanks to the very low backpressure generated from the silica column with low aqueous/high organic mobile phases, LC–MS/MS methods at high flow rates are feasible, resulting in significant timesaving. Because organic solvents have weaker eluting strength than water, direct injection of the organic solvent extracts from the reversed-phase solid-phase extraction onto the silica column was possible. Gradient elution on the silica columns using aqueous/organic mobile phases was also demonstrated. Contrary to what is commonly perceived, the silica column demonstrated superior column stability. This technology can be a valuable supplement to the reversed-phase LC–MS/MS.