Method for determining residual content of 4-methylpiperazine-1-formate genotoxic impurities in zopiclone

Abstract

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.

Description

technical field [0001] The invention belongs to the field of medicine technology, relates to the field of medicine impurity detection, in particular to a method for determining the residual content of 4-methylpiperazine-1-carboxylate genotoxic impurities in zopiclone, and the determined genotoxic impurity is 4-formazine Methyl piperazine-1-carboxylate, ethyl 4-methylpiperazine-1-carboxylate, isopropyl 4-methylpiperazine-1-carboxylate. Background technique [0002] Zopiclone (Zopiclone, ZOP), the chemical name is 6-(5-chloro-2-pyridyl)-7-[(4-methylpiperazin-1-yl) carboxyoxy]-5,6-dihydro Pyrrolo[3,4-b]pyrazin-5-one belongs to pyrrole cyclic ketone compounds, as a new type of non-benzodiazepine sedative hypnotics that has been used clinically, it can be effectively used in the treatment of insomnia Short term treatment. Racemic zopiclone has been marketed by the French company Rhone-Poulenc Rorer under the trade names IMOVANE and AMOBAN in more than 80 countries including Eur...

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Problems solved by technology

[0007] However, 4-methylpiperazine-1-carboxylic acid methyl ester, 4-methylpiperazine-1-carboxylic acid ethyl ester, 4-methylpiperazine-1-carboxylic acid ethyl ester, 4-methylpiperazine-1 -The inspection method for the residual content of isopropyl formate, the standard is missing, there are no relevant literature reports at home and abroad, it is impossible to evaluate the quality of the drug, and there are potential safety hazards

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