Objective: To evaluate the content of N-nitrosodimethylamine（NDMA）in metformin and its preparation by different methods. Methods: LC-MS/MS and GC-MS/MS methods were used to determine the content of NDMA in the solid preparations of metformin from four manufacturers and their metformin APIs. The difference of the results was compared and the NDMA increment of the preparation process was analyzed. Results: There was no difference between the two methods when no N-nitrosodimethylamine was detected in the samples（raw materials or preparations）. For the positive samples,the results of LC-MS/MS were all about 0.003 μg·g-1 higher than those of GC-MS/MS. The process increment was about 0.03 μg·g-1 for samples from company E,and there were great differences among different batches. There were no process increment for samples from company F,and different batches were stable. The process increment for samples from companies G and H was about 0.009 μg·g-1,and different batches were stable. Conclusion: There was no significant difference between LC-MS/MS and GC-MS/MS in the determination of NDMA in metformin APIs and their solid preparations. If there are nitrates in the excipients, NDMA can be produced in the preparations.
ZHANG Yan-chen, LIU Xiao-qiang, HUANG Hai-wei, LIU Min-hong, WANG Jia-li
. Different methods to evaluate the content of N-nitrosodimethylamine in metformin and its preparations[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(6)
: 1036
-1040
.
DOI: 10.16155/j.0254-1793.2021.06.14
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