STUDY OF BETA-CYCLODEXTRIN-KETOCONAZOLE-TARTARIC ACID MULTICOMPONENT NONCOVALENT ASSOCIATION BY POSITIVE AND NEGATIVE IONSPRAY MASS-SPECTROMETRY

In continuation of studies of multicomponent non-covalent associations (MCAs) of cyclodextrin (CD) inclusion or host-guest (H-G) complexes o f hydrophobic or barely water-soluble drugs with suitable counter ions , which can dramatically increase the hydrosolubility of the guest dru g, was the beta-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 posi tive IS mode a protonated 1 : 1 : 1 beta-CD-KC-TA gaseous species is o btained, which dissociates by the loss of TA upon collisional activati on (CA), thus reproducing the same behaviour as observed previously fo r a beta-CD-terfenadine-TA MCA. Unprecedented results were obtained in the negative ion mode. In particular, deprotonated 1 : 1 : 1 beta-CD- KC-TA MCA was detected, which upon CA yielded mainly deprotonated 1 : 1 beta-CD-TA and tartrate anion. Hence, while a relatively strong inte raction binding beta-CD to TA within the MCA parent anion emerges, the fair abundance of tartrate anion could suggest the formation of its n eutral complementary fragment, 1 : 1 beta-CD-KC, a possibly H-G comple x not observed as a negatively charged MS/MS fragmentation product. Th e role of the KC-TA ionic bonding of the neutral MCA appears very pert inent to the study by positive and negative ISMS of the non-covalent i nteractions within the gaseous protonated or deprotonated ternary comp lex thereof. (C) 1998 John Wiley & Sons, Ltd.