Abstract: OBJECTIVE To develop LC-MS method for the simultaneous determination of impurities A, C, and D of caspofungin acetate. METHODS Waters CORTECS^® C₁₈⁺(4.6 mm×150 mm, 2.7 μm) was used as the chromatography column. Mobile phase A and B were 0.1% formic acid-H₂O and 0.1% formic acid-CH₃CN, respectively. Electrospray ion source-single quadrupole mass spectrometry was used to detect impurities A and C in positive ion mode and impurity D in negative ion mode. RESULTS The correlation coefficient r was ≥ 0.999 in linearity ranges of impurities A, C and D. The average recoveries were 100.5%, 104.1% and 105.2%, respectively, with RSD<4%(n=6). The LOQs (S/N=10) of impurities A, C and D were 31.8, 6.99 and 15.5 ng·mL^-1 respectively. The contents of impurities A, C and D in the three samples were all below the limits. CONCLUSION The developed LC-MS method is simple, sensitive, and applicable, which can be used to simultaneously determine impurities A, C and D in caspofungin acetate and can also provide a reference for the detection of other impurities in caspofungin acetate.