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1.中国中医科学院 中药资源中心 道地药材国家重点实验室培育基地,北京 100700
2.云南中医药大学 中药学院,昆明 650500
3.齐鲁工业大学(山东省科学院) 山东省分析测试中心,济南 250014
4.中国中医科学院 中药研究所,北京 100700
5.中国中医科学院 博士后管理办公室,北京 100700
Received:06 June 2021,
Published Online:29 July 2021,
Published:20 June 2022
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张冠华,刘小莉,黄璐琦等.基质辅助激光解吸电离质谱法在中药领域的应用进展[J].中国实验方剂学杂志,2022,28(12):247-255.
ZHANG Guan-hua,LIU Xiao-li,HUANG Lu-qi,et al.Application of Matrix-assisted Laser Desorption Ionization Mass Spectrometry in Analysis of Traditional Chinese Medicine:A Comprehensive Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(12):247-255.
张冠华,刘小莉,黄璐琦等.基质辅助激光解吸电离质谱法在中药领域的应用进展[J].中国实验方剂学杂志,2022,28(12):247-255. DOI: 10.13422/j.cnki.syfjx.20211848.
ZHANG Guan-hua,LIU Xiao-li,HUANG Lu-qi,et al.Application of Matrix-assisted Laser Desorption Ionization Mass Spectrometry in Analysis of Traditional Chinese Medicine:A Comprehensive Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(12):247-255. DOI: 10.13422/j.cnki.syfjx.20211848.
中药具有丰富的化学成分和复杂的作用途径,在治疗和预防疾病方面疗效显著,为保证中药质量及开发新药,一些分析检测方法应运而生。基质辅助激光解吸电离质谱法(MALDI-MS)是一种“软电离”的新型质谱技术,具有高通量、高灵敏度、低成本、低样品消耗量、线性范围宽、电离温和、适用于热不稳定物质等特点,为中药的分子水平研究提供了技术支撑。目前该技术被广泛用于中药成分分析和组学研究领域,在药材真伪鉴别、分子实时筛选和构建活性成分的代谢网络途径方面发挥重要作用,其中,选择合适的基质和样品制备技术是保证检测效果的关键。随着新型基质的开发与优化、样品制备技术的不断完善、MALDI-MS与多种分析方法的联用,将会大幅提高其检测效果。基于此,笔者概述了MALDI-MS在中药领域的应用情况,包括高通量检测中药活性成分、监测机体内药物及其代谢物状况、原位可视化表征中药活性成分组织分布信息等,并探讨了MALDI-MS的应用前景和不足之处,以期为中药成分鉴定、药物利用及代谢的相关研究提供技术支撑。
Traditional Chinese medicine (TCM), which owns abundant chemical components and complex action pathways, has been widely recognized in the prevention and treatment of diseases. Some analysis methods have been emerged in order to ensure the quality of TCM and to develop new TCM drugs. Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) is a soft ionization mass spectrometric technique with the advantages of high throughput, high sensitivity, low cost and so on. It provides technical support for the molecular level study on TCM. At present, this technique has been used in the field of composition analysis and metabonomics research of TCM, and plays an important role in the identification of Chinese herbal medicines, real-time molecular screening and the construction of metabolic network pathway of active ingredients. Among them, the selection of appropriate matrix and sample preparation technology is the key to ensure the detection effect of MALDI-MS. With the development and optimization of new matrix, the continuous improvement of sample preparation technology and the combination of MALDI-MS with various analytical methods will greatly improve the detection effect. Based on this, this paper discusses the application of MALDI-MS in TCM, including high-throughput detection of active ingredients in TCM, monitoring of the original medicines and their metabolites
in
vivo
, and
in situ
visualization and characterization of tissue distribution information of active ingredients in TCM. It also discusses the application prospect and existing problems of MALDI-MS in TCM, so as to provide technical support for the identification of active ingredients in TCM, drug utilization and metabolism.
尹丽 , 宗兰兰 , 蒲晓辉 , 等 . 薄层色谱法在药物分析中的应用 [J]. 河南大学学报:医学版 , 2016 , 35 ( 2 ): 77 - 80 .
邓哲 , 荆文光 , 刘安 . 薄层色谱法在当前中药质量标准中的应用探讨 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 7 ): 201 - 206 .
梁晟 , 李雅文 , 赵晨曦 , 等 . GC-MS结合保留指数对中药挥发油的定性 [J]. 分析测试学报 , 2008 , 27 ( 1 ): 84 - 87 .
张辰露 , 吴三桥 , 秦文娟 , 等 . GC-MS法分析中药索骨丹中脂肪酸成分 [J]. 中国实验方剂学杂志 , 2012 , 18 ( 3 ): 100 - 102 .
吴文杰 , 周伟娥 , 张元 , 等 . LC-MS/MS技术在中药化学成分分析中的应用 [J]. 时珍国医国药 , 2016 , 27 ( 11 ): 2735 - 2737 .
何宝坤 , 杨明会 , 高月 . LC-MS联用技术在中药研究中的应用 [J]. 药物分析杂志 , 2007 , 27 ( 9 ): 1497 - 1500 .
陈子林 . 基于毛细管电泳-质谱联用的药物分析新方法 [C]// 中国化学会 . 第三届全国质谱分析学术报告会摘要集 : 2017年卷.厦门:中国化学会 , 2017 : 1 .
李佳佳 , 刘靖丽 , 靳如意 , 等 . 激光拉曼光谱分析中药复方制剂中青蒿素含量的研究 [J]. 光谱学与光谱分析 , 2019 , 39 ( 8 ): 2403 - 2408 .
秦海林 , 赵天增 . 核磁共振氢谱鉴别植物中药的研究 [J]. 药学学报 , 1999 , 34 ( 1 ): 59 - 63 .
KARAS M , HILLEBKAMP F . Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons [J]. Anal Chem , 1988 , 60 ( 20 ): 2299 - 2301 .
FEENSTARA A D , DUEÑAS M E , LEE Y J . Five micron high resolution MALDI mass spectrometry imaging with simple,interchangeable,multi-resolution optical system [J]. J Am Soc Mass Spectr , 2017 , 28 ( 3 ): 434 - 442 .
KOMPAUER M , HEILES S , SPENGLER B . Atmospheric pressure MALDI mass spectrometry imaging of tissues and cells at 1.4 μm lateral resolution [J]. Nat Methods , 2017 , 14 ( 1 ): 90 - 96 .
URBAN C , BUCK A , SIVEKE J T , et al . PAXgene fixation enables comprehensive metabolomic and proteomic analyses of tissue specimens by MALDI MSI [J]. Biochim Biophys Acta Gen Subj , 2017 , 1862 ( 1 ): 51 - 60 .
SUN C L , LI Z C , MA C X , et al . Acetone immersion enhanced MALDI-MS imaging of small molecule metabolites in biological tissues [J]. J Pharm Biomed Anal , 2019 , 176 : 112797 .
PEREIRA E M , MATTOS C , SANTOS O , et al . Staphylococcus hominis subspecies can be identified by SDS-PAGE or MALDI-TOF MS profiles [J]. Sci Rep , 2019 , 9 ( 1 ): 11736 .
STEVENSON L G , DRAKE S K , MURRAY P R . Rapid identification of bacteria in positive blood culture broths by matrix-assisted laser desorption ionization-time of flight mass spectrometry [J]. J Clin Microbiol , 2010 , 48 ( 2 ): 444 - 447 .
SAMARAH L Z , TRAN T H , STACEY G , et al . Mass spectrometry imaging of bio-oligomer polydispersity in plant tissues by laser desorption ionization from silicon nanopost arrays [J]. Angew Chem Int Ed Engl , 2021 , 60 ( 16 ): 9071 - 9077 .
WEI S D , ZHOU H C , LIN Y M , et al . MALDI-TOF MS analysis of condensed tannins with potent antioxidant activity from the leaf,stem bark and root bark of Acacia confusa [J]. Molecules , 2010 , 15 ( 6 ): 4369 - 4381 .
CHEN B M , MARISSA V , RICHARD G , et al . Combining MALDI mass spectrometry imaging and droplet-base surface sampling analysis for tissue distribution,metabolite profiling,and relative quantification of cyclic peptide melanotan Ⅱ [J]. Anal Chim Acta , 2020 , 1125 : 279 - 287 .
XU Y , DENG Y Z , YE R R , et al . MALDI-MS imaging of lipids and small molecules in rat brain tissue based on graphene oxide film pre-coated matrix [J]. Int J Mass Spectrom , 2021 , 464 : 116573 .
BALLUFF B , RAUSER S , MEDING S , et al . MALDI imaging identifies prognostic seven-protein signature of novel tissue markers in intestinal-type gastric cancer [J]. Am J Pathol , 2011 , 179 ( 6 ): 2720 - 2729 .
SUN C L , LIU W , MU Y , et al . 1,1'-Binaphthyl-2,2'-diamine as a novel MALDI matrix to enhance the in situ imaging of metabolic heterogeneity in lung cancer [J]. Talanta , 2020 , 209 : 120557 .
MAILHAC A , DURAND H , BOISSET S , et al . MALDI-TOF mass spectrometry for rapid diagnosis of postoperative endophthalmitis [J]. J Proteomics , 2017 , 152 : 150 - 152 .
SAUDEMONT P , QUANICO J , ROBIN Y M , et al . Real-time molecular diagnosis of tumors using water-assisted laser desorption/ionization mass spectrometry technology [J]. Cancer Cell , 2018 , 34 ( 5 ): 697 - 699 .
屈亮亮 . 基于MALDI的高通量蜂蜜糖浆掺假检测及植物源鉴别分析 [D]. 南昌 : 南昌大学 , 2020 .
袁湘林 , 张玉奎 , 邹汉法 . 基体辅助激光解吸电离飞行时间质谱用于中草药黄芪鉴别的研究 [J]. 药物分析杂志 , 2001 , 21 ( 1 ): 7 - 10 .
郑洁 . 胶类中药蛋白质的分析及鉴定研究 [D]. 镇江 : 江苏大学 , 2017 .
BEND J R , XUE Y X , CHEN D F , et al . Attenuation of oxidative stress in HEK 293 cells by the TCM constituents schisanhenol,baicalein,resveratrol or crocetin and two defined mixtures [J]. J Pharm Pharm Sci , 2015 , 18 ( 4 ): 661 - 682 .
PRIDEAUX B , STAAB D , STOECKLI M . Applications of MALDI-MSI to pharmaceutical research [J]. Methods Mol Biol , 2010 , 656 : 405 - 413 .
ZHU S H , SHIMOKAWA S I , TANAKA H , et al . Development of an assay system for saikosaponin a using anti-saikosaponin a monoclonal antibodies [J]. Biol Pharm Bull , 2004 , 27 ( 1 ): 66 - 71 .
KOULAKIOTIS N S , PITTENAUER E , HALABALAKI M , et al . Comparison of different tandem mass spectrometric techniques (ESI-IT,ESI-and IP-MALDI-QRTOF and vMALDI-TOF/RTOF) for the analysis of crocins and picrocrocin from the stigmas of Crocus sativus L [J]. Rapid Commun Mass Spectrom , 2012 , 26 ( 6 ): 670 - 678 .
SETHY N K , SINGH V K , SHARMA S , et al . Phytochemical and proteomic analysis of a high altitude medicinal mushroom Cordyceps sinensis [J]. J Proteins Proteom , 2016 , 7 ( 3 ): 187 - 197 .
LIU Y , LIU J Y , YIN P , et al . High throughput identification of components from traditional Chinese medicine herbs by utilizing graphene or graphene oxide as MALDI-TOF-MS matrix [J]. J Mass Spectrom , 2015 , 46 ( 8 ): 804 - 815 .
CAI Z , LEE F S , WANG X R , et al . A capsule review of recent studies on the application of mass spectrometry in the analysis of Chinese medicinal herbs [J]. J Mass Spectrom , 2002 , 37 ( 10 ): 1013 - 1024 .
刘芳 , 张琳 , 张志信 , 等 . 基质辅助激光解吸质谱成像在药用植物分析中的应用 [J]. 分析化学 , 2019 , 47 ( 8 ): 1125 - 1133 .
顾芹英 . 中药香椿叶化学成分的分离与分析 [D]. 镇江 : 江苏大学 , 2016 .
LI X H , YANG Y , YU Z , et al . Purification and identification of a novel protein isolated from Panax quinquefolium and evaluation of its in vitro antioxidant properties [J]. WJTCM , 2019 , 5 ( 4 ): 236 - 242 .
黄良 , 杨洪梅 , 石磊 , 等 . 以低浓度异甘草素为基质的MALDI-TOF MS用于小分子的检测研究 [J]. 质谱学报 , 2015 , 36 ( 3 ): 243 - 248 .
杨飞飞 . 中药多糖控制降解寡糖在中药鉴定中的应用研究 [D]. 保定 : 河北大学 , 2016 .
王莹 , 许玮仪 , 李丽潇 , 等 . 注射用黄芪多糖相对分子质量测定方法的比较及研究 [J]. 药学学报 , 2019 , 54 ( 2 ): 348 - 353 .
SAITO T , WATANABE A , NAKANO M , et al . MALDI-TOF mass spectrometry imaging for N -glycans on FFPE tissue sections of mouse NASH liver through sialic acid benzylamidation [J]. Glycoconjugate J , 2021 , 38 ( 2 ): 167 - 175 .
LAI Y H , SO P K , LO S C , et al . Rapid differentiation of Panax ginseng and Panax quinquefolius by matrix-assisted laser desorption/ionization mass spectrometry [J]. Anal Chim Acta , 2012 , 753 : 73 - 81 .
ZHU Z P , SHEN J J , XU Y F , et al . The improved performance of MALDI-TOF MS on the analysis of herbal saponins by using DHB-GO composite matrix [J]. J Mass Spectrom , 2019 , 54 ( 8 ): 684 - 692 .
鲁林 , 宋凤瑞 , 刘志强 . 人参皂苷成分的MALDI-TOF质谱分析 [C]// 中国质谱学会 . 中国有机质谱学第十四届全国学术大会会议论文集 : 2007年卷.上海:中国质谱学会 , 2007 : 2 .
WU W , QIAO C F , LIANG Z T , et al . Alkaloid profiling in crude and processed Strychnos nux-vomica seeds by matrix-assisted laser desorption/ionization-time of flight mass spectrometry [J]. J Pharm Biomed Anal , 2007 , 45 ( 3 ): 430 - 436 .
王勇 , 邓晓春 , 夏博 . 三种中成药中乌头生物碱飞行时间质谱分析 [J]. 深圳大学学报:理工版 , 2009 , 26 ( 3 ): 257 - 261 .
JABER A , SERAPHIN D , GUILET D , et al . Bithiophenic MALDI matrices as valuable leads for the selective detection of alkaloids [J]. Anal Bioanal Chem , 2017 , 409 ( 29 ): 6791 - 6801 .
ILBOUDO O , OUÈDRAOGO I W K , TAPSOBA I , et al . Analysis of flavonoid diglycosides in leaves of Mentha piperita L by MALDI-MS/MS and LC-MS [J]. Nat Prod , 2012 , 8 ( 8 ): 321 - 327 .
FOUGÈRE L , DA S D , DESTANDAU E , et al . TLC-MALDI-TOF-MS-based identification of flavonoid compounds using an inorganic matrix [J]. Phytochem Anal , 2019 , 30 ( 2 ): 218 - 225 .
LI B , GE J Y , LIU W , et al . Unveiling spatial metabolome of Paeonia suffruticosa and Paeonia lactiflora roots using MALDI MS imaging [J]. New Phytol , 2021 , 231 ( 2 ): 892 - 902 .
杨爱霞 , 张力凡 , 鲁力 . 黄芩苷磷脂复合物固体分散体的药动学研究 [J]. 中国药师 , 2020 , 23 ( 7 ): 1331 - 1334,1362 .
铁红云 , 商云霞 , 尉小慧 . 三七皂苷R 1 磷脂复合物的制备及其质量评价 [J]. 中国药学杂志 , 2020 , 55 ( 19 ): 1609 - 1615 .
刘会珍 , 董丹丹 , 范明松 . 不同厚朴酚制剂的制备、表征及其在SD大鼠体内药动学行为比较 [J]. 中草药 , 2020 , 51 ( 17 ): 4442 - 4448 .
赵玥祯 , 徐杨 , 龚灿 , 等 . 纳米四氧化三铁基质用于基质辅助激光解吸电离质谱法分析小分子化合物 [J]. 分析化学 , 2021 , 49 ( 1 ): 103 - 112 .
FUCHS B . Analysis of phospolipids and glycolipids by thin-layer chromatography-matrix-assisted laser desorption and ionization mass spectrometry [J]. J Chromatogr A , 2012 , 1259 : 62 - 73 .
SHI R , DAI X , LI W F , et al . Hydroxyl-group-dominated graphite dots reshape laser desorption/ionization mass spectrometry for small biomolecular analysis and imaging [J]. ACS Nano , 2017 , 11 ( 9 ): 9500 - 9513 .
TROENDLE F J , REDDICK C D , YOST R A . Detection of pharmaceutical compounds in tissue by matrix-assisted laser desorption/ionization and laser desorption/chemical ionization tandem mass spectrometry with a quadrupole ion trap [J]. J Am Soc Mass Spectrom , 1999 , 10 ( 12 ): 1315 - 1321 .
叶阿里 , 张海燕 , 窦亚玲 , 等 . 基质辅助激光解吸电离飞行时间质谱技术检测药物代谢酶基因多态性平台的建立 [J]. 现代检验医学杂志 , 2016 , 31 ( 5 ): 30 - 33 .
BARRY J A , GROSECLOSE M R , ROBICHAUD G , et al . Assessing drug and metabolite detection in liver tissue by UV-MALDI and IR-MALDESI mass spectrometry imaging coupled to FT-ICR MS [J]. Int J Mass Spectrom , 2015 , 377 : 448 - 155 .
刘芳 , 赵瀚森 , 孙公伟 , 等 . 基质辅助激光解析质谱成像可视化分析三七皂苷空间分布 [J]. 分析化学 , 2020 , 48 ( 7 ): 881 - 888 .
SUN C L , ZHANG M M , DONG H J , et al . A spatially-resolved approach to visualize the distribution and biosynthesis of flavones in Scutellaria baicalensis Georgi [J]. J Pharm Biomed Anal , 2020 , 179 : 113014 .
WANG S J , BAI H R , CAI Z W , et al . MALDI imaging for the localization of saponins in root tissues and rapid differentiation of three Panax herbs [J]. Electrophoresis , 2016 , 37 ( 13 ): 1956 - 1966 .
LI B , BHANDARI D R , JANFELT C , et al . Natural products in Glycyrrhiza glabra (licorice) rhizome imaged at the cellular level by atmospheric pressure matrix-assisted laser desorption/ionization tandem mass spectrometry imaging [J]. Plant J , 2014 , 80 ( 1 ): 161 - 171 .
SUN C L , LIU W , MA S S , et al . Development of a high-coverage matrix-assisted laser desorption/ionization mass spectrometry imaging method for visualizing the spatial dynamics of functional metabolites in Salvia miltiorrhiza Bge [J]. J Chromatogr A , 2020 , 1614 : 460704 .
孙成龙 , 刘伟 , 郭兰萍 , 等 . 基于MALDI质谱成像技术分析莲子中代谢物的组织分布 [J]. 分析测试学报 , 2021 , 40 ( 1 ): 86 - 91 .
LI B , NEUMANN E K , GE J Y , et al . Interrogation of spatial metabolome of Ginkgo biloba with high-resolution matrix-assisted laser desorption/ionization and laser desorption/ionization mass spectrometry imaging [J]. Plant Cell Environ , 2018 , 41 ( 11 ): 2693 - 2703 .
YANG S H , ZHAN L P , LIU C Z , et al . Mass spectrometry imaging of small molecule in situ in Lepidium meyenii (Maca) using gold nanoparticles matrix [J]. Microchem J , 2019 , 150 : 104190 .
WANG X N , TANG W W , GORDON A , et al . Porous TiO 2 film immobilized with gold nanoparticles for dual-polarity saldi ms detection and imaging [J]. ACS Appl Mater Interfaces , 2020 , 12 ( 38 ): 42567 - 42575 .
叶慧 , 王赟 , 王琳 , 等 . 基于MALDI-MS技术的新基质大黄酸在代谢组学研究中的应用 [J]. 中国药科大学学报 , 2016 , 47 ( 6 ): 727 - 733 .
MENG X Y , FU W Q , HUO M L , er al . In situ label-free visualization of tissue distributions of salidroside in multiple mouse organs by MALDI-MS imaging [J]. Int J Mass Spectrom , 2020 , 453 : 116347 .
聂宗秀 , 薛晋娟 , 刘会会 . 质谱成像技术对纳米载体原位药物释放的可视化研究 [C]// 中国化学会 . 第三届全国质谱分析学术报告会摘要集 : 2017年卷.厦门:中国化学会 , 2017 : 1 .
刘佳琦 , 杨琪 , 王沛 , 等 . 质谱成像技术在神经系统疾病药物研发中的应用 [J]. 神经药理学报 , 2019 , 9 ( 4 ): 60 - 61 .
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