米格列奈及其3个异构体杂质的反相液相色谱分离及质谱碎裂分析

引用本文: 李珉, 刘海涛, 侯金凤, 王成刚, 李文东, 车宝泉. 米格列奈及其3个异构体杂质的反相液相色谱分离及质谱碎裂分析[J]. 色谱, 2019, 37(4): 412-417. doi: 10.3724/SP.J.1123.2018.11046 shu

Citation: LI Min, LIU Haitao, HOU Jinfeng, WANG Chenggang, LI Wendong, CHE Baoquan. Reversed-phase liquid chromatography separation and mass spectrometry fragmentation analysis of mitiglinide and three isomers[J]. Chinese Journal of Chromatography, 2019, 37(4): 412-417. doi: 10.3724/SP.J.1123.2018.11046 shu

米格列奈及其3个异构体杂质的反相液相色谱分离及质谱碎裂分析

北京市药品检验所, 中药成分分析与生物评价北京市重点实验室, 北京 102206

摘要: 建立了超高效反相液相色谱-高分辨质谱方法以实现米格列奈及其3种异构体杂质的分离，以ACQUITY UPLC HSS T3（100 mm×2.1 mm，1.8 μ m）为色谱柱，以水-乙腈-正戊醇（75：25：1）（用甲酸调节pH至1.8）为流动相，流速为0.4 mL/min。根据Q Exactive四极杆/静电场轨道阱高分辨质谱的精确质量数及碎裂情况，发现了米格列奈及3种异构体存在碎片离子丰度的明显差异，确认其中两种为本次新发现的异构体杂质，并推断了米格列奈及3种异构体杂质可能的质谱裂解机理。经验证，该方法的灵敏度、重复性及线性均满足分析要求。在此基础上，对米格列奈异构体杂质的来源进行了探讨，发现异构体杂质1可在高温下降解产生，并对各企业的米格列奈钙原料样品进行了测定。

关键词:

English

Reversed-phase liquid chromatography separation and mass spectrometry fragmentation analysis of mitiglinide and three isomers

Beijing Institute for Drug Control, Beijing Municipal Key Laboratory for Analysis of Traditional Chinese Medicines and Biological Evaluation, Beijing 102206, China
Received Date: 30 November 2018

Abstract: The separation of mitiglinide and its three isomer impurities was achieved by reversed-phase ultra-performance liquid chromatography-high resolution mass spectrometry. An ACQUITY UPLC HSS T3 column (100 mm×2.1 mm, 1.8 μm) was used as the stationary phase and water-acetonitrile-n-pentanol (75:25:1, v/v/v; formic acid was added to adjust pH to 1.8) was used as the mobile phase with a flow rate of 0.4 mL/min. According to the exact mass and high resolution mass spectrometry fragmentation (Q Exactive), significant differences were observed in the fragment ion abundance in the secondary mass spectra of mitiglinide and its three isomer impurities. Two of these isomer impurities were newly discovered. The possible fragmentation mechanisms of mitiglinide and its three isomer impurities were also deduced. The limit of detection of the developed method was 1 μg/L. The linearity of the developed method was good from the limit of quantitation (2 μg/L) to 10000 μg/L with a correlation coefficient of 0.9999. The relative standard deviation of the peak area was 2.0%. On the basis of these results, the sources of the mitiglinide isomer impurities were discussed. Isomer impurity 1 was degraded at high temperature, while isomer impurities 2 and 3 were determined to be synthetic impurities. In addition, samples of mitiglinide calcium raw materials were analyzed.

Key words:

reversed-phase liquid chromatography (RPLC)
/ mass spectrometry (MS)
/ mitiglinide
/ isomers
/ fragmentation mechanism

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沈阳化工大学材料科学与工程学院沈阳 110142

米格列奈及其3个异构体杂质的反相液相色谱分离及质谱碎裂分析

English

Reversed-phase liquid chromatography separation and mass spectrometry fragmentation analysis of mitiglinide and three isomers

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

米格列奈及其3个异构体杂质的反相液相色谱分离及质谱碎裂分析

English

Reversed-phase liquid chromatography separation and mass spectrometry fragmentation analysis of mitiglinide and three isomers

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

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CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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