Quantitation of sulfobutyl ether-β-cyclodextrin (Captisol™) in Vestipitant IV solution by liquid chromatography with...

This work describes a simple, sensitive and fast liquid chromatographic method using ultraviolet (UV) detection for the quantitation of Captisol™ (sulfobutyl ether-β-cyclodextrin, SBE-β-CD) in Vestipitant (GW597599) IV formulation. The chromatographic system consists of a cyano-modified silica stationary phase column with 0.5mM copper(II) acetate in 50/50 (v/v) water/acetonitrile and 0.05% (v/v) of trifluoroacetic acid as the mobile phase. Due to the fact that SBE-β-CD does not possess a chromophore suitable for UV detection, copper(II) acetate is used as a detection reagent. At low pH copper(II) acetate interacts with SBE-β-CD and produces mixed copper(II) [Cu(2+)] chelate and copper(II) mono acetate [CuOAc(+)] complexes, while displacing sodium ions [Na(+)] from the sulfobutyl ether (SBE) group. The copper(II)-SBE-β-CD interaction has optical properties that allow its detection by UV. This novel method is highly reproducible and reliable for accurate quantitation of SBE-β-CD content in the Vestipitant IV solution, and in the solution without the Vestipitant matrix.