HPLC法测定硝酸咪康唑原料有关物质的研究

目的:利用高效液相法测定硝酸咪康唑原料中的4种已知杂质。方法:色谱柱为Venusil XBP C₁₈(150 mm×4.6 mm,5 μm),流动相:1.5%醋酸铵溶液-乙腈-甲醇(22∶38∶40);流速:1.0 mL·min^-1检测波长:230 nm;柱温:35 ℃。 结果:硝酸咪康唑原料中的4中已知杂质按照出峰顺序分别为α-(2,4-二氯苯基)-1H-咪唑-1-乙醇、2,4-二氯苯甲醇、2,4-二氯-β-[(2,4-二氯苯基)甲氧基]苯乙铵和N-[2-(2,4-二氯苯基)-2-[(2,4-二氯苯基)甲氧基]乙基]甲酰铵,4种已知杂质的相对响应因子(相对于硝酸咪康唑峰面积)分别为0.80, 0.77,1.06和1.00,4种已知杂质及硝酸咪康唑主峰均能有效分离,相互间最小分离度也可达到3.0以上。硝酸咪康唑原料的线性范围为:1~500 μg·mL^-1,相关系数为:0.9998。结论:该方法可作为控制硝酸咪康唑原料有关物质的质量标准。

Objective: To determine four related substances of miconazole nitrate by HPLC.Methods: The separation was performed on a Venusil XBP C₁₈ column(150 mm×4.6 mm,5 μm)with a mobile phase of 1.5% ammonium acetate solution-acetonitrile-methanol(22∶38∶40).The flow rate was 1.0 mL·min^-1 with column temperature at 35 ℃.The detection wavelength was 230 nm.Results: In accordance with the eluotropic sequence,four related substances were α-2,4-dichlorobenzene base-1 H-imidazole-1-ethanol,2,4-dichlorobenzene methanol,2,4-dichloro-beta-[(2,4-dichlorobenzene base)methoxyl] phenyl ethyl ammonium and N-[2 -(2,4-dichlorobenzene base)- 2-[(2,4-dichlorobenzene base)methoxyl] ethyl] formyl ammonium respectively.The correction factors of four related substances were 0.80,0.77,1.06 and 1.00.An excellent separation was achieved for miconazole nitrate and its four related substances with the minimum resolution over 3.0.The linear range of miconazole nitrate was 1~500 μg·mL^-1 and correlation coefficient was 0.9998.Conclusion: This method can be used as the quality control criteria of the related substances of miconazole nitrate raw materials.

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2 BP 2010.1433
3 EP6.0.2420
4 JP XV.892
5 USP 32.2981
6 Import drug registration standards JX20000233(进口药品注册标准JX20000233)
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