Determination of Low-ppm Levels of 1,4-Butane Sultone in Sulfobutyl Ether β-Cyclodextrin Using Liquid–Liquid Extraction and GC–MS

1,4-Butane sultone is an impurity in sulfobutyl ether β-cyclodextrin (SBE-β-CD), and has been reported to be a weak carcinogen. There is, however, no report of any method of determining 1,4-butane sultone in SBE-β-CD. In this paper, a gas chromatography–mass spectrometry (GC–MS) method was developed for the determination of 1,4-butane sultone. The samples were dissolved in water and extracted with chloroform. An Agilent DB-17MS column was used to separate the samples, and then the Agilent 5975B MS detector was employed. The selected ion monitoring mode (SIM: m/z 92, 120 for 1,4-butane sultone, m/z 54, 71, 106 for methyl salicylate—used as the internal standard) was used. The method showed a linear response across the concentration range 0.0256–1.024 μg mL−1 (r = 0.9997, n = 6). The detection limit of 1,4-butane sultone was found to be 12.8 ng mL−1, and the recovery (assessed via spiking) ranged from 96.28 to 100.45 %. The relative standard deviation of the precision for the proposed method was 2.68 %. The method developed here is fast and sensitive, and can be used to analyze the 1,4-butane sultone content of SBE-β-CD.