title: Equilibrium kinetics of the new experimental anti-tumour compound SK&F 104864-A in aqueous solution.
abstract: The equilibrium kinetics of lactone ring hydrolysis in the new experimental anti-tumour compound SK&F 104864-A. (S)-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride, have been studied. Only one product is formed, SK&F 105992. A stability-indicating HPLC method has been optimized to perform the analysis. The pH is the main factor influencing equilibrium; at pH greater than or equal to 10 the lactone ring is quantitatively opened while at pH values less than or equal to 4 the lactone form is exclusively present. Other parameters, such as buffer ions and ionic strength, do not influence equilibrium. Complexation with dimethyl-beta-cyclodextrin stabilizes the lactone form. Other cyclodextrins do not show this stabilization.
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Utrecht University, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: Underberg
authors.forename: R M
authors.initials: RM
authors.lastname: Goossen
authors.forename: B R
authors.initials: BR
authors.lastname: Smith
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D012996:Solutions; D013696:Temperature; D019772:Topotecan
chemical_list: D003505:Cyclodextrins; D012996:Solutions; D019772:Topotecan; D002166:Camptothecin