Objective: To establish a high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS/MS) method for the determination of N-dimethylnitrosamine(NDMA) in metformin hydrochloride drug substance and its products. Methods: The drugs were separated by Phenomenex ACE Excel 3 C18-AR column(100 mm×4.6 mm, 3 μm)with the mobile phases of 0.1% formic acid-water and 0.1% formic acid-methanol in gradient elution. The flow rate was 0.5 mL·min-1, and the column temperature was 40 ℃. The injection volume was 5 μL. The electrospray ionization source with positive ion mode was used for analyzing drugs in the multiple reaction monitoring mode. The transitions of m/z 75.0→43.0 and m/z 75.0→58.0 were determined as quantitative and qualitative ions respectively. Results: The linearity range of NDMA was 1-100 ng·mL-1and the detection limit was 0.25 ng·mL-1. The contents of NDMA in 30 batches were 0-0.46 μg·g-1. Conclusion: This method can be used for the quantitation of NDMA in metformin hydrochloride drug substance and its products.
ZHANG Long-hao, YU Ying-jie, YUAN Song, ZHOU Lu-ni, HUANG Hai-wei, HE Lan
. Method development for determination of genotoxic impurities N- dimethylnitrosamine in metformin hydrochloridey HPLC-MS/MS[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(7)
: 1195
-1200
.
DOI: 10.16155/j.0254-1793.2022.07.12
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