In recent years, it has been demonstrated that cluster ion beams may be used to sputter some materials, particularly organic materials, without the significant accumulation of damage. It is therefore possible to use cluster ion beam sputtering in conjunction with a surface analytical technique, such as SIMS, to obtain depth profiles and three-dimensional images of the distribution of organic species in the near-surface region. For SIMS organic depth profiling to be useful as an analytical tool, it is important that it is able to measure physically meaningful quantities, such as the local concentration of a species within a blend. In this paper, we investigate a model system of a miscible binary mixture of codeine and poly(lactide). We show that there is a strong surface enrichment of poly(lactide), which provides a reference signal and permits the direct comparison of different samples in terms of secondary ion yield behavior. We demonstrate that it is possible to relate secondary ion intensities to local concentrations for a binary system and that there is a direct correspondence between the yield enhancement of one component and the yield suppression of the other. The dependence of secondary ion yield on composition is described using a model of the kinetically limited transfer of charge between secondary ions and secondary neutrals. Application of the model to pure materials under the assumption that only highly fragmented secondary ions are initially produced and interact with unfragmented secondary neutrals leads to the prediction that high molecular mass quasi-molecular ions have intensities proportional to the square of the total secondary ion yield. This relationship has been independently observed in other work (Seah, M. P. Surf. Interface Anal. 2007, 39, 634.).