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

• Simple LC method using UV detection for the quantitation of SBE-β-CD is presented.
• Copper(II) acetate is used in the mobile phase as a detection reagent.
• At low pH mixed [Cu2+] chelate and [CuOAc+] complexes with SBE-β-CD are produced.
• Cyano-modified stationary phase with wide pore size provides SEC and RP mechanisms.

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 0.5 mM 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) [Cu2+] 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.

Coordination complexes of sulfobutyl ether-β-cyclodextrin with copper, Cu(II)-SBE-β-CD, have optical properties that enable their direct detection by UV, and are stable enough to be analyzed by HPLC. Because the complexation of SBE ligands with Cu(II) ions takes place outside the SBE-β-CD cavity, as well as within the cavity, a positive and a negative peaks are produced in the chromatogram. Cyano-modifed stationary phase with the wide pore size provides bimodal separation: size exclusion for the Cu(II)-SBE-β-CD complexes, since they occupy different hydrodynamic volumes; and reversed phase for the retention of the drug molecules. This can enable quantitation of both, the drug and the SBE-β-CD in a single chromatogram.Figure optionsDownload as PowerPoint slide