[Impurity profile study of cefalotin sodium by two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry].

A two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (2D-LC-QTOF MS) method to profile the impurities of cefalotin sodium was developed. A Symmetry C18 column (250 mm x 4.6 mm, 5 μm) was used in the first dimensional chromatography, with gradient elution using pH 2.5 phosphate buffer and acetonitrile as the mobile phases. The column temperature was maintained at 40 degrees C with an ultraviolet detection of 220 nm for analysis. An ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 μm) was used in the second dimensional chromatography, with gradient elution using water containing 0.1% (v/v) formic acid and acetonitrile containing 0.1% (v/v) formic acid as the mobile phases. The column temperature was maintained at 40 degrees C. An HLB C18 column (30 mm x 2.1 mm, 20 μm) was used as the trap column. The data were collected in positive ion mode. The ion source temperature was set at 100 degrees C and the electrospray ionization (ESI) needle voltage was set at 1 000 V. The nebulizer gas temperature was set at 500 degrees C. The molecular formulas of the impurities were determined by their exact masses and isotope distributions. And the structures were determined by the protonated molecular ions and the manufacturing process of cefalotin sodium. Six impurities of cefalotin sodium were characterized and the origination of the impurities was deduced. Three of them were unknown impurities to the best of our knowledge. It was confirmed that the Chinese Pharmacopoeia 2010 has mistaken impurity A of cefalotin sodium. The results indicated that the 2D-LC-QTOF MS method could be used to investigate the impurity profile of cefalotin sodium, and it is simple and sensitive.