LC-MS/MS法测定药用辅料磺丁基醚-β-环糊精中2个杂质

目的：建立高效液相离子对色谱-串联质谱法。测定磺丁基醚-β-环糊精（SBE-β-CD）中杂质4-羟基丁磺酸钠和二磺烷基化醚钠。方法：采用Inertsil ODS-SP C₁₈（4.6 mm×250 mm，5 μm）色谱柱；流动相为甲醇-10 mmol·L^-1正戊胺溶液（30：70），流速1.0 mL·min^-1。离子源：电喷雾离子（ESI）源；负离子多反应监测模式测定，4-羟基丁磺酸钠和二磺烷基化醚钠的监测离子对分别为m/z 153.0/79.8和m/z 289.0/152.9。结果：4-羟基丁磺酸钠和二磺烷基化醚钠分别在0.1~5.0 ng·mL^-1和0.4~20.0 ng·mL^-1范围内线性关系良好（r>0.999 6），定量限分别为0.01、0.04 ng·mL^-1，平均加样回收率分别为96.2%、95.4%，RSD分别为3.8%、4.1%。3批供试品中4-羟基丁磺酸钠的含量依次为0.001 6%、0.001 3%、0.000 57%，二磺烷基化醚钠均低于检测限。结论：该方法专属性强、灵敏度高，可用于4-羟基丁磺酸钠和二磺烷基化醚钠的测定，为SBE-β-CD的质量控制提供了便捷方法，同时也为其他烷基磺酸钠盐化合物的分析提供了参考。

Objective: To develop a method for the simultaneous determination of sodium 4-hydroxybutane-1-sulphonate and bis(4-sulfobutyl)ether disodium in betadex sulfobutyl ether sodium.Methods: An ion pair high performance liquid chromatography-mass spectrometry method(LC-MS/MS)was employed.Chromatographic separation was performed on an Inertsil ODS-SP C₁₈ column(4.6 mm×250 mm,5 μm) with isocratic elution of methanol-10 mmol·L^-1 amylamine aqueous solution(30:70)at a flow rate of 1.0 mL·min^-1.The detection was accomplished in the negative mode using multiple-reaction monitoring.The optimized mass ion-pairs for quantitation were m/z 153.0/79.8 and m/z 289.0/152.9 for sodium 4-hydroxybutane-1-sulphonate and bis(4-sulfobutyl)ether disodium,respectively.Results: The calibration curves were linear(r>0.999 6) within the range of 0.1-5.0 ng·mL^-1 for sodium 4-hydroxybutane-1-sulphonate and 0.4-20.0 ng·mL^-1 for bis(4-sulfobutyl)ether disodium,respectively.The LOQ were 0.01 and 0.04 ng·mL^-1;the average recoveries of the two compounds were 96.2% and 95.4% with relative standard deviations of 3.8% and 4.1% for sodium 4-hydroxybutane-1-sulphonate and bis(4-sulfobutyl)ether disodium,respectively.The contents of 4-hydroxybutane-1-sulphonate and bis(4-sulfobutyl)ether disodium in 3 batches of samples were 0.001 6%,0.001 3%,0.000 57% and below the detection limit,respectively.Conclusion: The LC-MS/MS method was developed to determine sodium 4-hydroxybutane-1-sulphonate and bis(4-sulfobutyl)ether disodium for the first time,which was specific,sensitive and suitable for quality control of betadex sulfobutyl ether sodium.It is also helpful to analyze other alkyl sulphonates.