Study of β-cyclodextrin-ketoconazole-tartaric acid multicomponent non-covalent association by positive and negative ionspray mass spectrometry

✍ Scribed by Selva, Antonio; Redenti, Enrico; Ventura, Paolo; Zanol, Margherita; Casetta, Bruno

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 240 KB
• Volume: 33
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/(sici)1096-9888(199808)33:8<729::aid-jms687>3.0.co;2-u

✦ Synopsis

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 b-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 b-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 b-CD-terfenadine-TA MCA. Unprecedented results were obtained in the negative ion mode. In particular, deprotonated 1 : 1 : 1 b-CD-KC-TA MCA was detected, which upon CA yielded mainly deprotonated 1 : 1 b-CD-TA and tartrate anion. Hence, while a relatively strong interaction binding b-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 b-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.