OBJECTIVE To determine nitrite in Metformin hydrochloride raw materials and excipients by Ion chromatography method,and to investigate the generation path of nitrosodimethylamine(NDMA)in its sustained-release tables.METHODS The content of nitrite in excipients was determined by Ion chromatography,while the content of dimethylamine in metformin hydrochloride raw material was determined by UPLC-MS,and the content of NDMA in Metformin hydrochloride sustained-release tables was determined by GC-MS.RESULTS A good linear relationship was obtained between the peak areas and the concentrations of nitrite(NO2-)in the range from 0.0165 g·mL-1 to 1.6450 g·mL-1.The detection limit of nitrite is 0.33 ng.The average recovery of raw materials was 93.6％,and the average recovery of excipients was 99.9％.Nitrite was not detected in the raw materials.However,the content of nitrite in excipients varied greatly,ranging from 1 ppm to 3 ppm.We found that nitrite in excipients and dimethylamine in raw materials could promote the production of NDMA.In addition,the production process of sustained-release tables and the storage process of sustained-release tables could lead to the increase of NDMA.CONCLUSION The method is accurate and sensitive,and can be used for the quality control of nitrite in metformin hydrochloride raw materials and excipients.It is suggested that the production enterprises should strictly control the content of nitrite in excipients and dimethylamine in raw materials,optimize the production process of sustained-release tablets,and prevent the high temperature during storage.
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