液相色谱-质谱联用鉴定他克莫司的有关物质

付晓婷; 陈民辉; 严菲; 杭太俊

doi:10.11665/j.issn.1000-5048.20220507

液相色谱-质谱联用鉴定他克莫司的有关物质

1.
江苏省食品药品监督检验研究院,南京 210019
2.
中国药科大学药学院，南京 210009

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出版历程
- 收稿日期: 2022-02-21
- 修回日期: 2022-09-14
- 刊出日期: 2022-10-24

Identification of the related substances of tacrolimus by LC-MS

1.
Jiangsu Institute for Food and Drug Control, Nanjing 210019
2.
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

摘要

摘要: 采用液相色谱-质谱（LC-MS）联用技术研究他克莫司的有关物质。采用Agilent Eclipse Plus-C₁₈（150 mm × 4.6 mm，3.5 μm）色谱柱，以0.01%甲酸水溶液-乙腈-甲基叔丁基醚为流动相体系，对他克莫司及其强制降解试验样品中的有关物质进行梯度洗脱分离；电喷雾正离子化-四极杆-飞行时间串联质谱法（ESI-Q-TOF/MS）测定各有关物质的母离子及碎片离子的准确质荷比和元素组成，并解析鉴定有关物质的结构。在所建立的条件下，他克莫司与其有关物质分离良好，检测并鉴定出35个主要有关物质，其中2个分别为他克莫司的互变异构体Ⅰ和Ⅱ（他克莫司的有效成分），3个为美国药典收载的已知杂质，其余30个为新鉴定的未知有关物质。研究结果可为他克莫司发酵生产过程的质量控制提供参考依据。
- 他克莫司 /
- 有关物质 /
- 降解产物 /
- 结构鉴定 /
- 液相色谱-质谱联用
Abstract: To identify the related substances of tacrolimus by LC-MS techniques, the separation of the related substances contained in tacrolimus and its stressed samples was carried out on a Agilent Eclipse Plus-C₁₈ (150 mm × 4.6 mm,3.5 μm) column with 0.01% fomic acid solution and a mixture of acetonitrile- methyl tert-butyl ether as the mobile phase.in linear gradient elution. Electrospray positive ionization high resolution Q-TOF/MS was used for the determination of the accurate mass and elemental composition of the parent ions of all the components, thence, the structures of all the detected substances were successfully characterized through spectra elucidation and fragmentation pathways analysis. Tacrolimus and its 35 detected related substances were well separated under the established conditions, among which 2 were its isomers , 3 were listed in United States Pharmacopeia(USP), and the rest 30 were identified as unknown products having not been reported before. These results were useful for its fermentation processes and quality control.
- tacrolimus /
- related substances /
- degradation products /
- structure identification /
- LC-MS

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参考文献(13)

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