Abstract: A method for the qualitative analysis of the composition of pharmaceutical excipient Span was established by ultra-high performance convergence chromatography-tandem quadrupole time-of-flight mass spectrometry (UPCC-QTOF-MS). The separation was performed on a VIRIDIS HSS C₁₈ SB 100A column (3.0 mm×150 mm, 18 μm) with gradient elution using CO₂ and isopropanol-tetrahydrofuran (98∶5) as the mobile phase. The column temperature was 50 °C. The flow rate was 1 mL/min. Isopropanol and 0.1 % formic acid aqueous solution (8∶2) were used as the compensation solvent. The back pressure was 13.78 MPa. The ionization mode was ESI ⁺, the acquisition mode was MS^E, and the m/z scanning range was from 100 to 1200. The samples of Span 20, 40, 60, 80 and 85 were determined respectively. The established method could distinguish the composition differences between different brands of Span, and it could analyze the components of different brands of Span as well. 21 components could be analyzed by Span 20, 7 by Span 40, 13 by Span 60, 9 by Span 80, and 9 by Span 85, and the structural analysis of each component was carried out. The method established in this paper can distinguish the composition differences between different brands of Span. It can also be used to analyze the composition and structure of different brands of Span. This method is green and environmentally friendly with guiding significance for Span quality control, process evaluation, and preparation application selection, etc.