The invention discloses a method for determining the residual contents of 4-methyl piperazine-1-methyl formate, 4-methyl piperazine-1-ethyl formate and 4-methyl piperazine-1-isopropyl formate in zopiclone. The method comprises the following steps: preparing a contrast solution: precisely weighing a proper amount of methyl 4-methylpiperazine-1-formate, a proper amount of ethyl 4-methylpiperazine-1-formate and a proper amount of isopropyl 4-methylpiperazine-1-formate, putting the weighed materials into a volumetric flask, dissolving the weighed materials with acetonitrile, diluting the dissolved materials, and respectively preparing 125ng / mL limit concentration solutions; preparing a test sample solution: precisely weighing a proper amount of zopiclone test sample, placing the zopiclone test sample in a volumetric flask, dissolving and diluting the zopiclone test sample with acetonitrile, and preparing the zopiclone test sample into a 1mg / mL solution; and sample determination: respectively taking the test solution and the reference solution, directly injecting the test solution and the reference solution into a GCMS, recording a chromatogram, and calculating by peak areas according to an external standard method to obtain the contents of the 4-methylpiperazine-1-methyl formate, the 4-methylpiperazine-1-ethyl formate and the 4-methylpiperazine-1-isopropyl formate in the test solution.