中国药物警戒 ›› 2023, Vol. 20 ›› Issue (12): 1326-1331.
DOI: 10.19803/j.1672-8629.20230587

• 临床药物质量监测及评价专栏 • 上一篇    下一篇

UPLC-Q-TOF-MS技术研究地平类药物成分质谱裂解规律

马春艳1, 宁霄2△, 段琼1, 胡伟杰1, 李景云2#, 张菁1*   

  1. 1河北省药品医疗器械检验研究院，河北 石家庄 050200;
    2中国食品药品检定研究院食品化妆品检定所，北京 100050
  • 收稿日期:2023-09-21 出版日期:2023-12-15 发布日期:2023-12-15
  • 通讯作者: *张菁,女,本科,主任药师,化妆品与药物分析。E-mail: 554392355@qq.com; #为共同通信作者。
  • 作者简介:马春艳,女,硕士,正高级工程师,化妆品与药物分析。△为并列第一作者。
  • 基金资助:
    国家重点研发计划（2021YFC2401100）; 河北省市场监督管理局科研计划（2021YJ07、2022ZC22）; 河北省中医药管理局科研计划（2024346）

Study on the mass spectrometric cleavage pattern of diphenhydramine constituents based on UPLC-Q-TOF-MS technology

MA Chunyan1, NING Xiao2△, DUAN Qiong1, HU Weijie1, LI Jingyun2#, ZHANG Jing1,*   

  1. 1Hebei Institute for Drug and Medical Device Control, Shijiazhuang Hebei 050200, China;
    2Institute for Food and Cosmetics Testing, National Institutes for Food and Drug Control, Beijing 100050, China
  • Received:2023-09-21 Online:2023-12-15 Published:2023-12-15

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摘要： 目的 探讨地平类药物在电喷雾质谱下的裂解途径,为该类成分的鉴定及结构分析提供参考。方法 采用Shim-packXR-ODS（100 mm×2.0 mm, 2.2μm）色谱柱,以0.1%甲酸溶液（A）- 0.1%甲酸乙腈（B）为流动相进行梯度洗脱,基于超高效液相色谱-四极杆-飞行时间质谱（UPLC-Q-TOF-MS）技术在正离子模式下对地平类药物（尼索地平、硝苯地平、尼莫地平、尼群地平、尼卡地平、非洛地平、氨氯地平）进行二级质谱分析,总结其裂解行为。结果 地平类药物成分在正离子检测模式下易发生质子化,形成[M+H]+的准分子离子,地平类化合物具有相似的裂解途径,在正离子模式下断裂过程主要集中在二氢吡啶母核附近的酯基基团或苯环上的取代基,形成特定的离子碎片（m/z 315.097 7、m/z 195.090 8和m/z 165.080 2）,即母离子脱去一分子的酯化基团-OR,继而丢失中性碎片取代苯基,在此基础上,再失去另一分子的酯化基团-OR,形成1,4-二氢吡啶的母核衍生形式。这些离子碎片可以较直观地表现母核上的取代基团,从而进一步体现地平类药物的分子结构。结论 本研究提出的电喷雾质谱裂解规律有助于对地平类化合物的结构进行解析与推断,可为该类成分的鉴定及结构分析提供参考。

关键词: 地平类药物, 二氢吡啶类药物, 液相色谱-四极杆-飞行时间质谱, 裂解规律, 鉴定, 结构分析

Abstract: Objective To explore the fragmentation pathway of dipyridamole compounds under the electrospray ionization mass spectrometry (ESI-MS), so as to provide a reference for the identification and structural analysis of these compounds. Methods A Shim-packXR-ODS (100 mm×2.0 mm, 2.2 μm) column was used for secondary mass spectrometry (MS/MS) analysis of dipyridamole (nisoldipine, nifedipine, nimodipine, nitrendipine, nicardipine, felodipine, amlodipine) in positive ion mode with a gradient elution of 0.1% formic acid solution (A) - 0.1% formic acid acetonitrile (B) as the mobile phases, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and the fragmentation behaviors of dipyridamole were summarized. Results The constituents of dipyridamole were easy to be protonated in the positive ion detection mode, forming quasi-molecular ions of [M+H]+. The dipyridamole compounds had similar cleavage pathways, and the fracture process in the positive ion mode mainly focuses on the ester groups near the parent nucleus of the dihydropyridine or the substituents on the benzene ring, forming specific ionic fragments (m/z 315.097 7, m/z 195.090 8, and m/z 165.080 2). That is, the mother ion removes one molecule of the esterification group - OR, and then loses the neutral fragment to replace the phenyl. On this basis, another molecule of the esterification group - OR is lost, forming a mother nucleus derived form of 1,4-dihydropyridine. These ion fragments can intuitively represent the substituent groups on the parent nucleus, thereby further reflecting the molecular structure of dipine drugs. Conclusion The electrospray mass spectrometry cleavage pattern proposed in this paper can help to analyze and deduce the structure of diphenhydramine compounds, which can provide a reference basis for the identification and structural analysis of these components.

Key words: dipyridamole compounds, dihydropyridine, UPLC-Q-TOF-MS, cleavage pattern, identification, structural analysis

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