This article describes a systematic study of ion release, carried out on lanthanide-encoded polystyrene-co-methacrylic acid (P(S-MAA)) and polystyrene-co-acrylic acid (P(S-AA)) copolymer particles, which were synthesized by two-stage or three-stage dispersion polymerizations. These particles with different levels of lanthanide (Ln) ion content and containing several different types of Ln ions were dispersed in normal buffer media, namely 2-(N-morpholino)ethanesulfonic acid (MES), phosphate buffered saline solution (PBS), ammonium acetate (AmAc) and buffers containing strong chelating molecules like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA). Traditional inductively coupled plasma mass spectrometry (ICP-MS) was employed to follow the loss of ions into the aqueous medium as a function of time. The release behavior of the Ln ions were compared. In MES and PBS buffers at neutral pH, and AmAc at pH 9.0, there was essentially no significant loss of Ln ions from the particles to the buffer. When the chelating agents EDTA or DTPA were present in the buffer, the loss of Ln ions was more prominent, but less than 15% after 8 weeks under stirring. The differences among the different samples were small. Considering the ability of EDTA and DTPA to remove Ln ions from the particles and the fact of minimal ion release in the presence of PBS buffer, we infer that the ion loss is a more active process involving the EDTA or DTPA molecules. The main conclusion is that in the absence of strong chelating agents, these particles are stable against ion leakage, even upon prolonged storage and stirring. This is of great importance for their application in bead-array biological assays based on mass cytometry detection. (C) 2011 Published by Elsevier Ltd.