摘要
目的 建立二甲双胍缓释片中N-亚硝基二甲胺(NDMA)的残留量的检测方法。方法 采用梯度洗脱法对二甲双胍缓释片中NDMA进行检测,流动相A为体积分数0.1%甲酸溶液,流动相B为甲醇;色谱柱为ACE C18-AR(4.6 mm×150 mm,3 μm);流速:0.5 mL·min-1;柱温为40 ℃;进样量:5 μL。接口电压:4 000 V;离子源温度:350 ℃;雾化气流量:15 L·min-1;加热气流量:35 L·min-1;辅助气流量0 L·min-1;定量离子对75.0/58.1;入口电压50 V;碰撞电压16 V。结果 方法学验证结果表明,方法线性良好, NDMA的精密度分别为101.00%,相对标准偏差(RSD)为5.3%(n=12),准确度分别为104.17%、97.67%和97.78%,RSD分别为1.9%、0.6%和1.3%(n=3)。定量限为1 ng·mL-1,检测限为0.3 ng·mL-1。结论 建立的液质联用检测方法快速、灵敏、重现性好的,可用于二甲双胍缓释片中NDMA的定量检测。
Abstract
OBJECTIVE To establish a method for the determination of N-nitrosodimethylamine (NDMA) residue in metformin hydrochloride sustained-release tablets. METHODS Gradient elution procedure was used for the determination of NDMA in metformin hydrochloride sustained-release tablets. The mobile phase A was 0.1% formic acid solution and mobile phase B was methanol. The chromatographic column was ACE C18-AR (4.6 mm×150 mm, 3 μm), the flow rate was 0.5 mL·min-1, the column temperature was maintained at 40 ℃, the injection volume was 5 μL. The interface voltage was 4 000 V, ion source temperature was 350 ℃, atomized gas flow was 15 L·min-1, heating gas flow was 35 L·min-1, auxiliary gas flow was 0 L·min-1, the quantitative ion pair was 75.0/58.1, inlet voltage was 50 V, and collision voltage was 16 V. RESULTS The results of methodological validation showed that the method had good linearity, the precision of NDMA was 101.00%, RSD was 5.3% (n=12), the accuracy was 104.17%, 97.67% and 97.78%, RSD was 1.9%, 0.6% and 1.3% (n=3), respectively. The quantitative limit was 1 ng·mL-1 and the detection limit was 0.3 ng·mL-1. CONCLUSION The established LC-MS method is rapid, sensitive, and reproducible, and can be used for the quantitative determination of NDMA in metformin hydrochloride sustained-release tablets.
关键词
二甲双胍缓释片 /
N-亚硝基二甲胺 /
液质联用法
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Key words
metformin hydrochloride sustained-release tablet /
N-nitrosodimethylamine /
HPLC-MS
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梁键谋, 蔡志威, 陈悦, 邵鹏, 李萍, 包鑫悠, 陈超.
液质联用法测定二甲双胍缓释片中亚硝基二甲胺的残留量[J]. 中国药学杂志, 2023, 58(19): 1769-1774 https://doi.org/10.11669/cpj.2023.19.007
LIANG Jianmou, CAI Zhiwei, CHEN Yue, SHAO Peng, LI Ping, BAO Xinyou, CHEN Chao.
Determination of N-Nitrosodimethylamine (NDMA) Residue in Metformin Hydrochloride Sustained-Release Tablets by HPLC-MS[J]. Chinese Pharmaceutical Journal, 2023, 58(19): 1769-1774 https://doi.org/10.11669/cpj.2023.19.007
中图分类号：
R917
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参考文献
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脚注
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基金
浙江省药品监管系统科技计划项目资助(2023003);浙江省科技计划项目资助(2022C01182)
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