Abstract: OBJECTIVE To establish a method for the simultaneous determination of twenty-one elemental impurities(Hg, As, Cd, Pb, Co, V, Ni, Li, Sb, Cu, Ba, Cr, Fe, Zn, Mn, Al, B, Ca, Mg, Si, Ti)in hydrocortisone injection by inductively coupled plasma mass spectrometry(ICP-MS). METHODS Standard addition method was employed, and samples were determined after dilution. With Ge, In, Bi as the internal standard elements, the contents of twenty-one elemental impurities in 67 batches of hydrocortisone injection and that in accelerated experimental samples were determined by ICP-MS. RESULTS Each element had a good linear relationship within the corresponding concentration range(r≥0.999 8). The recoveries were in the range of 96.10%-101.94%, with these RSDs <4.34%(n=9). The content of Al increased over time, but the daily intake of each element was below the permitted daily exposure. CONCLUSION This method is convenient, rapid, has good sensitivity and accuracy, and can be used for the determination of twenty-one elemental impurities in hydrocortisone injection.