In continuation of studies of multicomponent non-covalent associations (MCAs) of cyclodextrin (CD) inclusion or host–guest (H–G) complexes of hydrophobic or barely water-soluble drugs with suitable counter ions, which can dramatically increase the hydrosolubility of the guest drug, was the β-CD–KC–tartaric acid (TA) MCA, where KC=ketoconazole, an antifungal drug, investigated by ionspray (IS) mass spectrometry (MS) and MS/MS in both the positive and negative ion modes. In the positive IS mode a protonated 1:1:1 β-CD–KC–TA gaseous species is obtained, which dissociates by the loss of TA upon collisional activation (CA), thus reproducing the same behaviour as observed previously for a β-CD–terfenadine–TA MCA. Unprecedented results were obtained in the negative ion mode. In particular, deprotonated 1:1:1 β-CD–KC–TA MCA was detected, which upon CA yielded mainly deprotonated 1:1 β-CD–TA and tartrate anion. Hence, while a relatively strong interaction binding β-CD to TA within the MCA parent anion emerges, the fair abundance of tartrate anion could suggest the formation of its neutral complementary fragment, 1:1 β-CD–KC, a possibly H–G complex not observed as a negatively charged MS/MS fragmentation product. The role of the KC–TA ionic bonding of the neutral MCA appears very pertinent to the study by positive and negative ISMS of the non-covalent interactions within the gaseous protonated or deprotonated ternary complex thereof. © 1998 John Wiley & Sons, Ltd.