Abstract: OBJECTIVE To analyze caspofungin acetate and the samples under different strong degradation conditions by LC-QTOF-MS, and to study the characteristics in mass spectra of caspofungin and its related impurities(impurities A, B, C, D and E). METHODS Chromatographic separation was accomplished on Waters CORTECS^® C₁₈⁺(4.6 mm×150 mm, 2.7 μm) column using a gradient elution with monile phase of 0.1% formic acid-H₂O(A) and 0.1% formic acid-CH₃CN(B) at a flow velocity of 0.6 mL·min^-1; The analytes was detected in positive ion scan mode by ESI-QTOF-MS. RESULTS In MS¹ spectra, except that impurity D mainly showed single-charge quasi-molecular ion, caspofungin and the other four impurities showed muti-charge quasi-molecular ions with high abundance; In MS² spectra, caspofungin and its impurities that containing ethylenediamine generated fragment ions at m/z 1 033 by losing the ethylenediamine and the groups attached to it; caspofungin and its impurities produced a series of fragment ions mainly through the cleavage of peptide bonds, as well as through the loss of hydroxyl, acyl, or amino groups from amino acid residues; Impurity A and C showed characteristic fragment ions m/z 137.070 8 and m/z 77.071 1 with high abundance, respectively, which could be used to distinguish them from caspofungin and the other impurities. CONCLUSION Caspofungin and its five impurities have distict characteristics in their mass spectra. The research results can provide reference for identifying the structures of unknown impurities that may occur in the production process of caspofungin, so as to quickly discover the potential problems in the production process and reduce the quality risk of the products.