Analysis of sulfobutyl ether-β-cyclodextrin mixtures by ion-spray mass spectrometry and liquid chromatography–ion-spray mass spectrometry

The analysis of two commercial and two home-made sulfobutyl ether β-cyclodextrin (SBE-β-CD) samples by ion-spray (IS) mass spectrometry and by liquid chromatography–mass spectrometry coupling (LC–MS) is investigated in a negative ion mode. SBE-β-CD fragmentation was first investigated by direct infusion. In IS, the best conditions for SBE-β-CD ionization consisted of ammonium acetate added to an acetonitrile/water mixture as sample solvent. These conditions allowed simplification of the mass spectrum, mainly by the formation of dicharged species [M–2H]2−, thus limiting the production of multicharged fragments. IS-MS permits fast and simple measurement of the substitution pattern and determination of the global degree of substitution for SBE-β-CD mixtures. A complementary method using LC–MS was developed for the analysis of these mixtures. The substitution patterns obtained by LC–MS are in good agreement with those determined by direct MS analysis. The LC–MS coupling enabled separation of the mixtures versus the charge in anion-exchange chromatography (AEC) whereas no separation of the different substitution isomers potentially present in the SBE-β-CD mixture was displayed. The AEC methodology described can be successfully used for fractionation of SBE-β-CD derivatives at the semi-preparative scale.