Effects of platinum silicon, graphite and PET substrates on the secondary ion yield of sub-monolayer and multilayer samples of Cyclosporin A following 20 keV Au+, Au-3(+) and C-60(+) impacts have been investigated. The obtained results of sub-monolayer samples show that platinum enhances the yield of the pseudo-molecular ion following Au+ and Au-3(+) impacts due to the high density of the substrate that enables the energy of the primary ions to be deposited near the surface. C-60(+) impacts on sub-monolayer samples are less effective, but there is an enhancement on PET substrates. Impacts of 20 keV Au+ and Au-3(+) are not very efficient on multilayer samples. 20 keV C-60(+) impacts enhance the yields significantly, especially for the relatively high molecular weight [M+H](+) ion. (c) 2008 Elsevier B.V. All rights reserved.