UPLC-DAD-MS法测定普伐他汀钠及其制剂中的有关物质

Analysis of related substances in pravastatin sodium and its preparations by UPLC-DAD-MS

目的:建立UPLC-DAD-MS法测定普伐他汀钠及其制剂中的有关物质,确定杂质结构。方法:采用C_(18)色谱柱(2.1 mm×100 mm,1.7μm),流动相A为水-p H 7.0缓冲液-乙腈(52∶30∶18),流动相B为乙腈-p H 7.0醋酸铵缓冲液-水(60∶30∶10),梯度洗脱,检测波长238 nm;采用质谱检测系统,ESI离子源,正离子扫描模式。收集来自4个厂家的普伐他汀钠原料、5个厂家的普伐他汀钠片和1个厂家的普伐他汀钠胶囊,对其中的杂质进行测定。结果:结合各杂质的质谱、光谱和色谱信息,共鉴定6种已知杂质。通过强制降解试验,明确各杂质来源。测定各杂质的响应因子,确定各杂质的计算方法,并测定普伐他汀原料及其制剂的有关物质含量。不同来源普伐他汀钠原料中的单个杂质含量为0.06%~0.80%,总杂质含量为0.11%~1.70%,不同来源普伐他汀钠制剂中的单个杂质含量为0.08%~2.61%,总杂质含量为0.38%~3.20%。结论:建立的液相色谱-质谱联用测定方法可用于测定普伐他汀钠及其制剂中的杂质,为工艺考察和质量控制提供参考。

Objective：To develop a UPLC-DAD-MS method for determination of related substances in pravastatin and its preparations to identify the structures of impurities. Methods：The analyte was gradient eluted on a C18 column（2.1 mm×100 mm,1.7 μm）with mobile phase A[water-p H 7.0 buffer solution-acetonitrile（52∶30∶18）]and mobile phase B[acetonitrile-p H 7.0 buffer solution-water（60∶30∶10）]. The detection wavelength was 238 nm. Electrospray ionization source was operated in positive ion mode.Related substances were determined in samples of pravastatin sodium substance from four manufacturers,pravastatin sodium tablets from five manufacturers and pravastatin sodium capsules from one manufacturer. Results：Six impurities were indentified according to chromatogram,spectrum and mass spectrum information. Impurity resource was elucidated through multiple degradation tests. Correction factors of impurities were determined and the calculation method was confirmed. The contents of related substances in pravastatin sodium and its products were determined. The contents of single impurity in pravastatin sodium substance from different manufacturers were 0.06%-0.80%;and the contents of total impurities were 0.11%-1.70%. The contents of single impurity in pravastatin sodium preparations from different manufacturers were 0.08%-2.61%;and the contents of total impurities were 0.38%-3.20%. Conclusion：The UPLC-MS/MS method can be used for determination of related substances in pravastatin and its preparations. It can provide the reference for manufacture process and quality control of pravastatin sodium.