色谱-质谱联用技术鉴定盐酸咪达唑仑的有关物质

金瑞; 闫若凝; 陆宇婷; 宋敏; 杭太俊

doi:10.11665/j.issn.1000-5048.20200309

色谱-质谱联用技术鉴定盐酸咪达唑仑的有关物质

中国药科大学药物分析系，南京 210009

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出版历程
- 收稿日期: 2020-03-24
- 修回日期: 2020-04-27
- 刊出日期: 2020-06-24

Identification of related substances of midazolam hydrochloride by LC-MS

摘要

摘要: 色谱-质谱联用（LC-MS）技术鉴定盐酸咪达唑仑中的有关物质。采用Thermo BDS Hypersil C₁₈ (100 mm×4.6 mm，2.4 μm)色谱柱，以乙腈-25 mmol/L醋酸铵水溶液(冰醋酸调节pH为5.5)为流动相梯度洗脱，对盐酸咪达唑仑有关物质进行分离，电喷雾正离子化-四极杆-飞行时间串联质谱(ESI-Q-TOF/MS)高分辨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，通过光谱解析并结合合成工艺分析鉴定了它们的结构，并对部分杂质进一步采用对照品对照确证。在所建立的分析条件下，盐酸咪达唑仑及其有关物质分离良好，检测并鉴定出盐酸咪达唑仑及其强制降解试验样品中22个主要有关物质，其中8个为美国药典规定的已知杂质。LC-MS技术能有效地分离鉴定盐酸咪达唑仑中的有关物质，可为其贮存条件制定、生产工艺优化和质量控制提供参考依据。
- 盐酸咪达唑仑 /
- 有关物质 /
- 结构鉴定 /
- 色谱-质谱联用
Abstract: This study aimed to identify the related substances of midazolam hydrochloride by liquid chromatography-mass spectrometry (LC-MS). To separate the related substances of midazolam hydrochloride, gradient elution was performed using acetonitrile and 25 mmol/L of ammonium acetate (pH was adjusted to 5.5 with acetic acid) as mobile phase on Thermo BDS Hypersil C₁₈ column (100 mm × 4.6 mm, 2.4 μm). The accurate mass and elemental composition of the parent ions and their product ions of related substances were determined by electrospray-ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF/MS). The structures of the related substances were identified by spectral analysis and process synthesis, and some of them were further confirmed by reference substances. Under the established HPLC condition, midazolam hydrochloride and its related substances were adequately separated, and 22 major related substances were detected and identified by hyphenated techniques in midazolam hydrochloride and its stressed samples, of which 8 were recorded as impurities in the United States Pharmacopeia. The LC-MS techniques can effectively separate and identify the related substances of midazolam hydrochloride and provide reference for the establishment of storage condition, optimization of synthetic processes and quality control.

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参考文献(19)

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色谱-质谱联用技术鉴定盐酸咪达唑仑的有关物质

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Identification of related substances of midazolam hydrochloride by LC-MS

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