Determination of N-Nitrosodimethylamine (NDMA) Residue in Metformin Hydrochloride Sustained-Release Tablets by HPLC-MS
LIANG Jianmou1, CAI Zhiwei1,2, CHEN Yue1, SHAO Peng1, LI Ping3, BAO Xinyou4, CHEN Chao1*
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1. Key Laboratory of Drug Contacting Materials Quality Control of Zhejiang Province, Zhejiang Institute for Food and Drug Control, Hangzhou 310052, China; 2. Institute of Chemistry, University of Strasbourg, Strasbourg 67081, France; 3. Zhejiang University of Technology, Hangzhou 310014, China; 4. Hangzhou Medical College, Hangzhou 310053, China
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.
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
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