The influence of the flow cell configuration on the mass spectra obtained when coupling an electrochemical thin-layer flow cell to electrospray mass spectrometry (ESI-MS) has been investigated. It is shown that interferences due to the electrochemical reaction on the counter electrode and/or the absence of 100% conversion efficiency can alter the mass spectra when conventional thin-layer flow cells are used in conjunction with ESI-MS. The effects, which affect the intensities and distribution of the peaks in the mass spectra, can result in the inability to detect products formed at the working electrode. Comparisons of mass spectra, generated after the electrochemical [Mn-2(II,II)(bpmp)(mu-OAc)(2)](+) (where bpmp = 2,6-bis[bis(2-pyridylmethyl) amino]methyl-4-methylpheoxidation of a dinuclear Mn complex using two different thin-layer flow cells clearly show that the potential dependence and appearance of the mass spectra depend on the flow cell configuration used. The use of a modified thin-layer flow cell, in which the counter electrode had been separated from the working electrode, gave rise to significantly increased intensities for the oxidised Mn-III,Mn-IV state of the complex. With the conventional unmodified cell, the corresponding complex was only seen for considerably higher oxidation potentials. The different results can be explained by the reduced risk of redox cycling and interferences due to species generated at the counter electrode with the modified cell. As interferences due to the counter electrode reactions likewise may be expected with many coulometric flow cells, the electrochemical cell design clearly needs to be considered when using electrochemistry coupled to ESI-MS to study electrochemical reactions. (c) 2006 Elsevier B.V. All rights reserved.