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目的建立测定异丙托溴铵原料药中有关物质的高效液相色谱–二极管阵列检测器–质谱(HPLC-DAD-MS)法。方法采用HPLC-MS法,Alltima C_(18)色谱柱(150 mm×4.6 mm,5μm);流动相:0.01 mol/L乙酸铵–乙腈,梯度洗脱;体积流量:0.25 m L/min;柱温:35℃,进样量:10μL;检测波长:220 nm。采用离子阱(ESI)正负离子模式进行检测,源温110℃;脱溶剂温度350℃;脱溶剂气体积流量600 L/h;锥孔气体积流量50 L/h。结果异丙托溴铵、托品酸、托品酸乙酯和杂质F在0.01~10.00、0.012~12.000、0.083~8.300、0.05~5.00 mg/m L显示良好的线性关系;异丙托溴铵、托品酸、托品酸乙酯和杂质F的最低检测限分别为1.46、0.57、4.16、5.03 ng;异丙托溴铵、杂质C、托品酸乙酯和杂质F的定量限分别为4.38、1.71、12.48、15.09 ng。结论该方法灵敏度高、选择性高、检测限低,为异丙托溴铵的质量控制提供依据。
OBJECTIVE To establish a high performance liquid chromatography-diode array detector-mass spectrometry (HPLC-DAD-MS) method for the determination of related substances in ipratropium bromide drug substance. Methods The HPLC-MS method was used on Alltima C 18 column (150 mm × 4.6 mm, 5 μm). The mobile phase consisted of 0.01 mol / L ammonium acetate-acetonitrile gradient elution. The volume flow rate was 0.25 m L / Temperature: 35 ℃, injection volume: 10μL; detection wavelength: 220 nm. The ion source (ESI) positive and negative ion mode was used for detection. The source temperature was 110 ℃, the desolvation temperature was 350 ℃, the volume flow rate of desolvation gas was 600 L / h and the volume flow of cone gas was 50 L / h. Results Ipratropium bromide, tropic acid, ethyl propionate and impurity F showed a good linearity in the range of 0.01-10.00,0.012-12.000,0.083-8.300,0.05-5.00 mg / ml; that of ipratropium bromide , And the limits of detection of tropic acid, ethyl palmitate and impurity F were 1.46,0.57,4.16 and 5.03 ng, respectively. The limits of quantification of ipratropium bromide, impurity C, ethyl palmitate and impurity F were 4.38, 1.71, 12.48, 15.09 ng. Conclusion The method has high sensitivity, high selectivity and low detection limit, which provides the basis for the quality control of ipratropium bromide.