AbstractThe coupling of column liquid chromatography on‐line with mass spectrometry using post‐column phosphate suppression is described. A membrane suppressor is used to remove the non‐volatile phosphate ions from the mobile phase after the chromatographic separation prior to introduction into the mass spectrometer. Using post‐column phosphate suppression by a membrane device phosphate concentrations up to 10 mM phosphate, at a mobile phase flow rate of 0.1 ml/min, could be removed for more than 99% without any decay of the sensitivity of the MS detection.Using a new antidepressant tetracyclic basic compound, ORG 4428, and some structure related compounds as model compounds electron impact as well as chemical ionisation spectra of all compounds could be obtained. The set‐up could be used for several weeks running, using a phosphate containing mobile phase, without any loss of pe