N2-DART-Orbitrap中的特征气相离子反应及在西药快速检测中的应用

doi:10.7503/cjcu20160645

高等学校化学学报 ›› 2017, Vol. 38 ›› Issue (3): 362.doi: 10.7503/cjcu20160645

N₂-DART-Orbitrap中的特征气相离子反应及在西药快速检测中的应用

施晓宇¹, 苏蕊¹(), 杨洪梅¹, 连文慧¹, 万茜淋¹, 刘淑莹^1,²

1. 长春中医药大学吉林省人参科学研究院, 长春 130117
2. 中国科学院长春应用化学研究所, 长春 130022

收稿日期:2016-09-19 出版日期:2017-03-10 发布日期:2017-02-22
作者简介:联系人简介: 苏蕊, 女, 博士, 助理研究员, 主要从事复杂基质的质谱分析研究. E-mail: sranalchem@163.com
基金资助:
吉林省科技厅重点科技攻关项目(批准号: 20160204027YY)、吉林省教育厅“十三五”科学技术研究项目(批准号: 吉教科合字[2016]第002号)和国家自然科学基金(批准号: 21305135)资助.

Detection of Pharmaceuticals by Nitrogen Direct Analysis in Real Time Mass Spectrometry^†

SHI Xiaoyu¹, SU Rui^1,^*(), YANG Hongmei¹, LIAN Wenhui¹, WAN Xilin¹, LIU Shuying^1,^2,^*

1. Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China
2. Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China

Received:2016-09-19 Online:2017-03-10 Published:2017-02-22
Contact: SU Rui,LIU Shuying E-mail:sranalchem@163.com
Supported by:
† Supported by the Project of Science and Technology Department of Jilin Province, China(No.20160204027YY), the Project of the Education Department of Jilin Province, China(No.2016002) and the National Natural Science Foundation of China(No.21305135).

摘要/Abstract

摘要：

采用实时直接分析(DART)离子源串联高分辨质谱Orbitrap技术(DART-Orbitrap MS), 对8种市售常见西药进行有效成分分析, 建立了一种快速、简便、准确测定西药中有效成分的方法. 对DART离子源的离子化温度、扫描模式、操作气体种类、辅助溶剂种类及其酸碱性等实验条件进行了优化, 得到最佳实验条件. 实验结果表明, 正谱条件下, 采用N₂气作为操作气体时, 待测组分准分子离子峰[M+H]⁺同样具有较高的灵敏度和谱图辨识度. 因此, N₂气可以替代昂贵的He气作为DART离子源的操作气体用于8种药物有效成分的现场实时检测. 该方法具备成本低、快速和操作简便的特点. 通过分析待测组分的特征碎片离子, 发现了N₂-DART离子源中的特征离子反应, 包括氧化反应和重排反应. 根据获得的特征碎片离子对N₂-DART-MS中发生的反应机理进行推导, 并结合理论计算对其进行验证. N₂-DART-MS技术有望应用于复杂基质混合物的现场快速检测中.

关键词: 实时直接分析(DART)离子源, Orbitrap高分辨质谱, 药物有效成分, 快速检测

Abstract:

Direct analysis in real time-mass spectrometry(DART-MS) was usually employed as a novel method for fast screening of target compounds in complex matrix samples. However, nitrogen direct analysis in real time(N₂-DART) mass spectrometry(MS) analysis of labile compounds usually tends to be challenging because of its low ionization energy and complex background signals. In the current study, N₂-DART ion source coupled with high resolution Orbitrap MS based on a make-up solvent approach, which was designed for analysis of pharmaceuticals sensitively and easily, was reported. The main parameters of ion source, including gas temperature, gas type, scan mode, and solvent effect, were studied. The results confirmed that, compared with conventional He-DART, N₂-DART could generate obviously different ions in positive ion mode. And the sensitivity obtained by N₂-DART was found to be comparable with that obtained by He-DART. Typical mechanisms including the reactions of oxidation and rearrangement in N₂-DART were also discussed in detail. For the purpose of further confirmation, theoretical calculation was employed to verify the feasibility of the rearrangement reaction. The results demonstrated that N₂-DART-MS could provide a rapid and reliable method for the identification of active ingredients in pharmaceuticals, and may be applicable to other mixtures.

Key words: Direct analysis in real time(DART), Orbitrap MS, Active ingredients of pharmaceuticals, Rapid detection

中图分类号:

O654

TrendMD:

施晓宇, 苏蕊, 杨洪梅, 连文慧, 万茜淋, 刘淑莹. N₂-DART-Orbitrap中的特征气相离子反应及在西药快速检测中的应用. 高等学校化学学报, 2017, 38(3): 362.

SHI Xiaoyu, SU Rui, YANG Hongmei, LIAN Wenhui, WAN Xilin, LIU Shuying. Detection of Pharmaceuticals by Nitrogen Direct Analysis in Real Time Mass Spectrometry^†. Chem. J. Chinese Universities, 2017, 38(3): 362.

图/表 6

Table 1 Ion information of the 8 selected pharmaceuticals in positive ion mode

Designation	Molecular formula	Molecular mass	Precursor ion	Intensity	Fragment ion	Fragment energy/eV
Chlorpheniramine maleate	C₂₀H₂₃ClN₂O₄	390.1346	275.1303 [M-C₄H₄O₄+H]⁺	2.38×10⁸	230.0727	23
Loratadine	C₂₂H₂₃ClN₂O₂	382.1448	383.1521 [M+H]⁺	2.07×10⁸	337.1109,267.0815	45
Dextromethorphan hydrobromide	C₁₈H₂₅NO·HBr· H₂O	369.1303	272.2005 [M-HBr·H₂O+H]⁺	2.88×10⁸	213.1278,171.0809	40
Terfenadine	C₃₂H₄₁NO₂	471.3137	472.3210 [M+H]⁺	7.00×10⁷	436.3011,454.3087	25
Cimetidine	C₁₀H₁₆N₆S	252.1157	253.1230 [M+H]⁺	4.27×10⁷	159.0703	28
Paeonol	C₉H₁₀O₃	166.0630	167.0703 [M+H]⁺	1.95×10⁷	117.0481	65
Acetaminophen	C₈H₉NO₂	151.0633	152.1406 [M+H]⁺	4.07×10⁷	121.0654,149.0602	55
Butyl flufenamate	C₁₈H₁₈F₃NO₂	337.1290	338.1362 [M+H]⁺	2.64×10⁸	135.1173	18

Fig.1 N2-DART orbitrap mass spectra of 8 pharmaceuticals in positive ion mode (A) Chlorpheniramine maleate; (B) loratadine; (C) dextromethorphan hydrobromide; (D) terfenadine; (E) cimetidine; (F) paeonol; (G) acetaminophen; (H) butyl flufenamate.

Fig.2 Mass spectra of loratadine obtained using helium(A), argon(B) and nitrogen(C) as DART carrier gas

Fig.3 Influence of three solvents with different concentrations on signal intensities obtained for cimetidine in positive ion mode Data points are mean values of three determinations.

Fig.4 Probable fragmentation mechanism in N2-DART MS (A) Oxygen addition products of cimetidine; (B) oxygen addition product of paeonol; (C) rearrangement reactions of paeonol; (D) rearrangement reaction of chlorpheniramine maleate; (E) dehydration reaction of terfenadine.

Fig.5 Potential energy diagrams for the fragmentation and rearrangement reaction of paeonol

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N₂-DART-Orbitrap中的特征气相离子反应及在西药快速检测中的应用

Detection of Pharmaceuticals by Nitrogen Direct Analysis in Real Time Mass Spectrometry^†

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