Stabilization of an anthrapyrazole antitumour agent, DuP 937, on complexation with heptakis(2,6-di-O-methyl)-beta-cyclodextrin in aqueous solution.
DuP 937, an anthrapyrazole antitumour agent that is chemically unstable in aqueous solution, was shown, by absorption spectroscopy, to form an inclusion complex with heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM beta CD) in aqueous solution. Proton nuclear magnetic resonance spectroscopy was used to determine the stoichiometry and association constant of the complex. The 1:1 stoichiometry of the complex was established by the continuous variation method by following changes in the chemical shifts of aromatic protons of DuP 937. The complex association constants determined by different techniques used in this study were in the same order of magnitude. The kinetics of degradation of DuP 937 in aqueous solution were investigated as a function of DM beta CD concentration at pH 5.5 and 60 degrees C. The results indicated about a seven-fold increase in the stability of DuP 937 in the presence of DM beta CD in aqueous solution.
Raghavan
K
K
DuPont Merck Pharmaceutical Co., Experimental Station, Wilmington, DE 19880-0400.
Nemeth
G
G
Gray
D
D
Hussain
M A
MA
D000880:Anthraquinones / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D002853:Chromatography, Liquid; D003505:Cyclodextrins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D047392:beta-Cyclodextrins
D000880:Anthraquinones; D000970:Antineoplastic Agents; D003505:Cyclodextrins; D007202:Indicators and Reagents; D011720:Pyrazoles; D047392:beta-Cyclodextrins; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; C046658:teloxantrone