The adsorption behavior of ammonium hexafluorophosphate was studied on four HPLC columns packed with adsorbents of different ability for dispersive interactions using frontal chromatography with LC/MS detection in negative ESI mode. Hexafluorophosphate (PF6−) adsorption isotherms were measured from acetonitrile/water and methanol/water mixtures. Increased PF6− adsorption with increased acetonitrile content was found between 0 and 15% of acetonitrile in the eluent. Further increase of the acetonitrile concentration leads to an exponential decrease of PF6− adsorption. Methanol, on the other hand, causes a steady decrease of PF6− adsorption with increased organic concentration in the mobile phase.