Objective: To confirm the structure of four degradation impurities of menadione sodium bisulfite injection using UPLC-Q-Orbitrap HRMS. Methods: UPLC was applied with a Thermo Gold C18 column(100 mm×2.1 mm,1.9 μm) and eluted with 0.02 mol·L-1 ammonium acetate solution-methanol (92∶8). MS was applied with HESI source and positive/negative ion modes. Fragment analysis was carried out by Mas Frontier7.0 software. The structures of four degradation impurities in the injection of menadione sodium bisulfite were characterized and confirmed. Results: Four degradation impurities,which were sodium 3-(hydroxymethyl) -1,4-dioxo-1,4-dihydronaphthalene-2-sulfonate (impurity 1),sodium 1-hydroxy-3-methyl-4-oxo-1, 2,3,4-tetrahydronaphthalene-1,3-disulfonate (impurity 2),sodium 4-hydroxy-3-methyl-1-oxo-1, 2-dihydronaphthalene-2-sulfonate (impurity 3) and sodium 1,4-dihydroxy-3-methylnaphthalene-2-sulfonate (impurity 4), were confirmed. This study used analytical methods such as HPLC-PDA,UPLC-HRMS,and 1HNMR. The degradation mechanism was proposed and confirmed by organic synthesis,forced degradation etc. Conclusion: Through the structure study of the degradation impurities and the mechanism of tautomerism and auto-oxidation,this method provides a reference for the process optimization and quality control of sodium bisulfite menadione injection.
CHENG Jie, LI Xian-qing, WANG Jing-jing, XIE Zi-li, DU Wei-feng
. Qualitative analysis of 4 degradation impurities in menadione sodium bisulfite injection by UPLC-Q-Orbitrap HRMS*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(9)
: 1538
-1549
.
DOI: 10.16155/j.0254-1793.2021.09.07
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