目的: 采用二维液相色谱-质谱联用技术鉴定地氯雷他定中的有关物质。方法: 采用Waters Symmetry C8（250 mm×4.6 mm, 5 μm）色谱柱,以1%三乙胺10 mmol · L-1磷酸二氢钾溶液（磷酸调pH至2.0）-乙腈-甲醇（80∶10∶10）为流动相A,1%三乙胺10 mmol · L-1磷酸二氢钾溶液（磷酸调pH至2.0）-乙腈-四氢呋喃（30∶70∶5）为流动相B,线性梯度洗脱,对地氯雷他定有关物质进行第一维液相色谱分离。各分离成分经多通道切换阀分别被捕集于截留管中,然后输送到Thermo BDS Hypersil C18（100 mm×4.6 mm, 3 μm）色谱柱,以10 mmol · L-1乙酸铵溶液-甲醇为流动相,进行第二维液相色谱梯度洗脱实现快速脱盐后,电喷雾正离子化-四极杆-飞行时间高分辨质谱测定各有关物质母离子及其子离子的准确质量和元素组成,通过光谱解析鉴定其结构。结果: 在所建立的分析条件下,地氯雷他定及其有关物质分离良好,检测并鉴定出地氯雷他定及其强制降解试验样品中12个有关物质,其中3个为已知杂质,其他杂质为新鉴定杂质。结论: 二维液相色谱-质谱联用可以在保持地氯雷他定有关物质检查的非挥发性流动相分离的条件下,实现其有关物质的专属鉴定,研究结果可为地氯雷他定质量控制提供参考。
Objective: To identify the related substances in desloratadine using two-dimensional liquid chromatography-mass spectrometry (2D LC-MS) technology. Methods: A Waters Symmetry C8 column (250 mm×4.6 mm, 5 μm) was employed. The mobile phase A consisted of a mixture containing 1% triethylamine and 10 mmol · L-1 potassium dihydrogen phosphate solution adjusted to pH 2.0 with phosphoric acid, acetonitrile, and methanol (80∶10∶10), while mobile phase B contained 1% triethylamine, 10 mmol · L-1 potassium dihydrogen phosphate solution (pH adjusted to 2.0 with phosphoric acid), acetonitrile, and tetrahydrofuran (30∶70∶5). A linear gradient elution was used for the first-dimension liquid chromatography separation of related substances in desloratadine. Individual separated components were captured through a multi-channel switching valve into retention vessels, then transferred to a Thermo BDS Hypersil C18 column (100 mm×4.6 mm, 3 μm). After a second-dimension gradient elution with a mobile phase composed of 10 mmol · L-1 ammonium acetate solution and methanol to achieve rapid desalting, electrospray ionization positive ionization-quadrupole-time-of-flight high-resolution mass spectrometry was employed to measure the accurate masses and elemental compositions of parent ions and their daughter ions of the related substances. Structural identification was achieved through spectral analysis. Results: Under the established analytical conditions, desloratadine and its related substances were well separated. A total of 12 related substances were detected and identified in desloratadine and its stressed degradation samples. Among these 12 degradants, three were known impurities, while the others are newly identified impurities. Conclusion: 2D LC-MS can effectively provide specific identification of desloratadine’s related substances under non-volatile mobile phase separation conditions. The findings from this study serve as a reference for controlling the quality of desloratadine.
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