The new analytical method of very high pressure liquid chromatography (VHPLC) has been designed for the estimation of related substances in bisoprolol fumarate. Several columns filled with sub-2-μm totally porous and shell adsorbent have been tested and compared during the method development. The columns' resolution was investigated. The shell adsorbent appears to have smaller resolution than the totally porous adsorbent. The tips and recommendations for the HPLC-VHPLC method transfer are presented. Significant reduction in analysis run time and solvent consumption has been obtained.