注射用奥美拉唑钠有关物质测定及杂质谱研究

Study on Determination and Impurity Profile of Related Substances of Omeprazole Sodium for Injection

关键词:  奥美拉唑  有关物质  杂质  高效液相色谱  测定

Key words:  omeprazole  related substances  impurities  HPLC  determination

摘要:

目的 通过对注射用奥美拉唑钠中有关物质的定性和定量分析,研究注射用奥美拉唑钠的杂质谱。方法 采用ACES-AQ色谱柱(4.6 mm×250 mm,5 μm),以磷酸盐缓冲液(pH 7.0)-乙腈(75:25)为流动相A,乙腈为流动相B,进行梯度洗脱,流速为1.0 mL·min^-1,检测波长为280 nm。采用加校正因子的主成分自身对照法对注射用奥美拉唑钠中的12个已知杂质及4个未知杂质进行分离和定量测定。采用超高效液相色谱-三重四极杆质谱联用法对4个未知杂质进行结构推测。结果 奥美拉唑与其有关物质分离良好,9个杂质的校正因子在0.48~1.14,不同企业注射用奥美拉唑钠检出3~8个杂质。结论 所建的方法专属性好,可有效地分离和测定注射用奥美拉唑钠中的有关物质。本研究为注射用奥美拉唑钠的杂质控制提供科学参考。

Abstract:

OBJECTIVE To study the impurity profile of omeprazole sodium for injection by qualitative and quantitative analysis on the related substances of it. METHODS Chromatographic separations were performed on an ACES-AQ column(4.6 mm×250 mm, 5 μm). The gradient elution employed solutions A and B as mobile phase components. The solvent A was phosphate buffer (pH 7.0)-acetonitrile(75:25), while solvent B was acetonitrile. The mobile phase was pumped at 1.0 mL·min^-1. The detection wavelength was 280 nm. Twelve known impurities and other four unknown impurities in omeprazole sodium for injection were quantitatively determined by principal component self-control method with correction factor. The structures of four unknown impurities were inferred by high-performance liquid chromatography-triple quadrupole mass spectrometry. RESULTS Omeprazole and its related substances had good separation. The correction factors of nine impurities ranged from 0.48 to 1.14. Three to eight impurities were detected in omeprazole sodium for injection produced from different enterprises. CONCLUSION The developed method with good specificity can be used for the separation and determination of related substances in omeprazole sodium for injection and can help for the impurity control of omeprazole sodium for injection.