The administration of high doses of Methotrexate (HDMTX) seems to be very effective in neoplastic treatment. Furthermore high doses of the drug could overcome the Methotrexate (MTX) resistance that it is possible to observe in some kind of cancers. To avoid several serious problems in the therapeutical application of HDMTX such as nephrotoxicity, hepatotoxicity and the difficulty to assess the right therapeutic range of the specific antagonist Leucovorin, a Haemoperfusion (HP) treatment could be very usefulL. In this study 3 anion exchange resins with different active group (trimethylammonium, dimethylethanolammonium and dimethylammina) and a spherical petroleum based charcoal were tested both in vitro and ex vivo to evaluate their capability to remove MTX. These results show a good strength and biocompatibility of the 4 sorbents and demonstrate the active group trimethylammonium resin as the most effective one.