碘海醇中有关物质O-烷基化合物和N-烷基化合物的质谱分析

Identification for related substances of O-alkyl compounds and N-alkyl compounds in iohexol by HPLC-MS/MS

目的:鉴定碘海醇中保留时间在碘海醇外异构体之后的有关物质。方法:采用Sycronis C_(18)(100 mm×2.1 mm,3.0μm)色谱柱,以0.01%甲酸水溶液为流动相A,甲醇为流动相B,梯度洗脱,采用基于静电场轨道阱(Orbitrap)技术的质谱法,根据精确分子量和一级、二级裂解规律,对保留时间在碘海醇之后有关物质的色谱峰进行质谱分析。结果:精确分子量表明,这些有关物质或是O-烷基化合物或是N-烷基化合物;裂解规律表明,O-烷基化合物更容易形成m/z 803.877 0碎片离子和m/z 166.107 38碎片离子;N-烷基化合物可形成m/z 112.075 69、m/z 104.070 60和m/z 86.060 04碎片离子;据此推测出有关物质1~5为N-烷基化化合物,有关物质6~11为O-烷基化合物。结论:研究结果可为碘海醇质量标准修订和检测结果的判断提供科学、合理和可靠的依据。

Objective：To identify the related compounds with retention time after iohexol exo-isomer in iohexol.Methods：Sycronis C_（18）（100 mm×2.1 mm,3.0 μm）column was adopted,gradient elution was completed by using 0.01% formic acid solution as mobile phase A and methanol as mobile phase B,and the related compounds with retention time after iohexol were analyzed according to their molecular weight and the cleavage mechanism of their mass spectra were analyzed by using HPLC-MS/MS based on the Orbitrap technology.Results：These related compounds are attributed to N-alkyl compounds or O-alkyl compounds according to their accurate molecular weight,and the mass spectra cleavage mechanism shows that the O-alkyl compounds are easier to form characteristic fragmental ions withm/z 803.877 0 and m/z 166.107 38,while the N-alkyl compounds are able to form characteristic fragmental ions with m/z 112.075 69、m/z 104.070 60 and m/z 86.060 04.Therefore the related compounds 1-5 are assigned to N-alkyl compounds and the related compounds 6-11 are O-alkyl compounds.Conclusion：The findings may be used as the scientific,reasonable and reliable evidence for quality standards revision and judgment of the test results on iohexol.Keywords diagnosis with drugscontrast agentCT scan drugsiohexolalkyl compoundsrelated substances