Objective: To establish a liquid-liquid extraction method for the determination of genotoxic impurities N-nitrosodimethylamine(NDMA) and N-nitrosodiethylamine(NDEA) in chondroitin sulfate sodium by gas chromatography-mass spectrometry (GC-MS). Methods: The chromatographic column was Thermo TG WAXMS (30 m × 0.25 mm,0.25 μm). The column temperature was maintained at 40 ℃ for 1 min, increased to 240 ℃ at 25 ℃·min-1 and maintained for 2 min. The inlet temperature was 220 ℃. The carrier gas was high-purity helium, and the flow rate was 1.0 mL·min-1. The ion source of mass spectrometry was EI source. The electron energy was 70 eV. The ion source temperature was 280 ℃ and the transmission line temperature was 240 ℃. Injection volume was 1 μL. Results: The LOD of NDMA was 0.64 ng·mL-1. Experiment showed a good linear relationship between peak area and concentration in the range of 4-16 ng·mL-1, and the correlation r was 0.999 3. The LOD of NDEA was 0.176 ng·mL-1 with a good linear relationship between peak area and concentration within the range of 1.1-4.4 ng·mL-1. The correlation r was 0.999 6. NDMA and NDEA were not detected in chondroitin sulfate sodium. Conclusion: The method is simple, specific and can be used to determine the genotoxic impurities NDMA and NDEA in chondroitin sulfate sodium.
ZAN Yan-nan, SHANG Shao-hua, CHEN Ning, DING Yi-mei
. Determination of genotoxic impurities N-nitrosodimethylamine and N-nitrosodiethylamine in chondroitin sulfate sodium raw materials by liquid-liquid extraction/GC-MS[J]. Chinese Journal of Pharmaceutical Analysis, 2024
, 44(3)
: 462
-467
.
DOI: 10.16155/j.0254-1793.2024.03.11
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