In miniaturized liquid chromatography (LC) an online clean up system and/or pre-concentration step, is essential to increase large loading capacity, loading speed could be used so the analysis is faster, and it is more robust (i.e. sample cleanup of salts and excess reagents. In this study the goal was to make efficient and robust reversed phase (RP) silica-based monolithic pre-columns with an inner diameter (ID) of ≤50 µm to be used in a switching system with an online pre-column. The silica skeleton was found to be the trickiest part to make in these columns, because they easily shrink and crack. Different procedures were investigated and a procedure was found to give the thinnest skeleton (0.4 µm) without shrinking/cracking. The solutions found to give the most homogenous skeleton was obtained with this procedure: Pre-treated and silanized fused silica capillaries were filled with a polymerization solution consisting of 4.5 mL tetramethoxysilane (TMOS), 1.06 g polyethylene glycol (PEG) (Mn = 10 000) and 10 mL aqueous acetic acid (0.01 M), which was allowed to react at 40 oC for 24 h. The capillary was subsequently filled with ammonium hydroxide (0.1 M) and allowed to react at 120 oC for 3h, before the skeleton was dried at 330 oC for 24 h. The reason for absence of shrinking/cracking was the final heating step at 330 oC. A “thiol-ene” click reaction was found to be an easy way to link the stationary phase (SP) to the skeleton. First vinylfunctionalization of the skeleton was carried out with vinyltrimethoxysilane (VTMS) followed by a click reaction with octanethiol, that gave a RP column with C8 as SP. Columns with plate height down to 70 µm were made, tested with a simple LC-UV system. One of the columns was successfully implemented in an LC-Mass Spectrometry (MS) system as a pre-column in combination with a 50 µm x 15 cm Accucore (2.6 µm) RP analytical column. A peak capacity of 79 was obtained, compared to a system with a commercial packed pre-column that gave a peak capacity of 47(measured at half peak height). Many procedures presented in papers were investigated and they are not good enough to reproduce a successful silica- based monolithic column.