Method Validation and Monitoring of N-nitrosodimethylamine in Metformin Hydrochloride Products in China by GC-MS/MS

作者全名："Zou, Jia-jia; Yang, Lin; Xu, Xiao-li; Li, Yan; He, Dan"

作者地址："[Zou, Jia-jia; Xu, Xiao-li; He, Dan] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Yang, Lin; Li, Yan] Chongqing Med & Pharmaceut Coll, Chongqing Pharmaceut Preparat Engn Technol Res Ctr, Chongqing 401331, Peoples R China"

通信作者："He, D (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China."

来源：CURRENT PHARMACEUTICAL ANALYSIS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001152194700003

JCR分区：Q4

影响因子：0.7

年份：2023

卷号：19

期号：10

开始页：759

结束页：766

文献类型：Article

关键词：Genotoxic impurity; NDMA; determination; GC-MS/MS; metformin hydrochloride; products

摘要："Background: N-nitrosodimethylamine (NDMA) are a sort of genotoxic impurities (GTIs) having strong carcinogenic effects and obvious hepatotoxicity. To monitor the NDMA content of metformin hydrochloride sustained-release tablets and enteric capsules in China from 2018 to 2022, a GC-MS/MS method was established and validated. Materials and Methods: The chromatographic column was Agilent VF-WAXms capillary column (30 mx0.25 mm, 0.25 mu m). The GC-MS/MS method was equipped with multiple reaction monitoring (MRM) modes. To assess the quantity of NDMA, the molecular ion at mass-to-charge (m/z) of 74-44 was monitored under the 6 V collision energy, and to assess the quality of NDMA monitoring, the molecular ions at m/z 74-42 were determined. A total of 143 batches of metformin hydrochloride-finished products from 35 enterprises were determined by this method. Results: The linear range of the method was 0.25 similar to 50.00 ng/mL, r = 0.9998, S/N > 10, and the limit of detection and quantitation were 0.06 ng/mL and 0.21 ng/mL, respectively. The average recovery was 98.62%, and the RSD was 4.31%. All batches of enteric capsules met the requirements; 38.21% of the 123 batches sustained-release tablets still exceeded the acceptable daily intake. Conclusion: The presented method is sensitive, accurate, precise, and available for both enteric capsules and sustained-release tablets of metformin hydrochloride, which can provide a reference for their quality control. The over-limit phenomenon of NDMA in metformin hydrochloride products poses new challenges and requirements for both the State Drug Administration and enterprises."

基金机构：Chongqing Medical University Personnel Support Program [YXY2021SDTR01]

基金资助正文：This research was supported by grants from the Chongqing Medical University Personnel Support Program (YXY2021SDTR01)