An ESI-MS method for the determination of host-guest association constants and binding selectivities for systems of binary and complex mixtures, respectively, is presented in an effort to quantitatively study the strength of host-guest interactions, while accounting for the different ESI-MS spray efficiencies of each component. Association constants were obtained for host-guest complexes formed between a series of crown ether and linear ionophore hosts and various guests, including protonated amines, and an apo- and ferri-siderophore, ferrioxamine B. © 2009 Springer Science+Business Media B.V.