A study by ionspray, Fast atom bombardament, and tandem mass spectrometry of 1:1 melatonin/BETA-cyclodextrin inclusion complex

Cyclodextrins (CDs) are the natural oligosaccharides of general use for the preparation of non-covalent inclusion or host-guest complexes of scientific and technological relevance. Such complexes, are of current interest to the pharmaceutical industry whereas they can improve hydrosolubility, stability and bioavailability of the hosted drugs. Melatonin (MLT)is the pineal hormone regulating circadian rhythms. The aromatic portion of its molecular structure appears suitable for the inclusion into the hydrophobic cavity of CDs. Actually, the formation of a water­ soluble 1:1 beta-CD/MLT host-guest complex by mixing the two components in equimolecular ratio was supported by high-resolution NMR measurements in D2O and by other experimental evidence. As a part of a research programme on CDs complexes of biologically interesting molecules, we present the preliminary results of a study of this beta-CD/MLT host-guest complex by ionspray (IS) or fast atom bombardment (FAB} ionization mass spectrometry (MS) and by tandem-MS, operating in positive ion mode and using triple quadrupole analyser. A solid sample, obtained by freeze-drying a water solution of the 1:1 beta-CD/MLT host-guest complex, was dissolved in a 1:1 (v/v) water/acetonitrile or in thioglycerol and submitted to IS or FAS ionization, respectively. Our preliminary findings showed that: i) both IS and FAB ionization allowed to detect fairly abundant gaseous protonated 1:1 beta­ CD/MlT species from the related host-guest association in condensed phase; ii) in tandem MS CID the proton (charge) was retained by the host, which also underwent marked beta-CD cage fragmentation, more than by the guest; iii) FAB likely generated complex parent species with apparent internal energy excess, according to the fragmentation even without collision gas; in such conditions the proton was mostly retained by MLT product.