样品预处理与实时直接分析质谱的联用技术及应用

近年来,与实时直接分析质谱(DART-MS)相结合的样品预处理技术发展迅速,使得对复杂生物、环境、法医学、食品、个体小生物以及单细胞样品中的分析物进行直接分析成为可能。然而固体基质内部分析物检测困难、痕量分析物检测性能不佳已成为限制DART-MS进一步发展的关键问题。针对这些问题,多年来,研究人员在不同领域对样品预处理与质谱联用进行了多种尝试。该文以固相萃取(SPE)、分散固相萃取(DSPE)、搅拌棒吸附萃取(SBSE)、固相微萃取(SPME)、机械化学提取(MCE)和微波提取(MAE)等样品预处理技术为例,对不同研究领域中样品预处理技术与DART-MS联用的研究成果进行了综述,并对未来的发展趋势进行了展望。希望该综述能为开发与DART-MS联用的新型样品处理技术提供参考和帮助。     

原位电离与小型质谱在公共安全领域的应用

质谱作为一种具有高准确度、高灵敏度、高选择性的检测仪器,在公共安全领域有着重要的应用前景。公共安全领域的需求主要涉及毒品、毒物、爆炸物等化学物质的现场快速检测,因其影响广泛,检测结果需非常准确。作为实验室分析仪器,质谱的准确性和速度能满足公共安全的应用需求,但作为现场快速检测的仪器仍需要一定改进。现场快速检测一方面要求检测仪器的小型化,另一方面要求样品前处理的简单化,以使整个检测流程可以无需专业人员来完成。对于检测仪器的小型化,小型质谱的开发在近20年得到了充分发展;对于样品前处理的简单化,研究者发明了原位电离技术,使得基质复杂的被分析物无需前处理即可进行质谱检测。该文首先介绍了原位电离技术的发展及其在公共安全领域的应用,特别是对解吸附电喷雾电离、实时直接分析电离、激光烧蚀电喷雾电离、纸喷雾电离与纸毛细管喷雾电离等典型原位电离技术的原理、性能及在公共安全领域的应用进行了详细介绍,并讨论了几种原位电离现场定量方法。然后,对原位电离小型质谱的发展进行了综述,从最初的小型化离子阱,到仅能检测可挥发有机物的小型质谱,再到可检测非挥发性物质的常规大气压电离源小型质谱,最后发展成为有原位电离源的小型质谱,历经20年的发展使得原位电离小型质谱得以出现和提升。并列举了原位电离小型质谱在毒品现场检测与吸毒人员排查、爆炸物现场侦察、食品安全之农用化学品检测、药物质量检查等公共安全领域的应用。最后,对原位电离小型质谱的发展进行了展望,指出原位电离与小型质谱相结合是小型质谱发展的必然趋势,未来需使用更加智能化的原位电离小型质谱,结合云数据平台,实现更方便广泛的应用。     

快速蒸发电离质谱技术及其应用研究进展

近年来,原位电离质谱技术成为质谱分析领域的研究前沿和热点。快速蒸发电离质谱技术源于外科手术中的手术烟雾现象,自2009年报道以来,作为一种新型原位电离质谱技术已被广泛应用于医学、微生物鉴定、食品真伪鉴别、代谢物研究、药用植物成分鉴定等领域。该技术通过电离切割组织或其他生物样品产生的含丰富特定区域生物特征的气溶胶,对其进行原位、在线、实时、快速质谱分析。该文阐述了快速蒸发电离质谱技术的发展历程、电离机制及工作原理,并对其在不同领域的应用研究进展进行了综述,可为相关领域研究人员提供科研思路和技术参考。     

薄层色谱与质谱联用的研究进展

薄层色谱(TLC)是一类非常实用的液相色谱方法,由于其装置简单、操作便捷、灵活、通量高、成本低,以及样品前处理简单等优点,在许多行业的检测中都有广泛的应用并扮演着重要的角色。随着现代检测技术的不断发展以及各种检测技术综合应用程度的加深,薄层色谱与质谱的联用(TLC-MS)也成为这一方法的重要发展方向。随着我国医药、食品、科学仪器等事业的不断发展和升级,相信薄层色谱-质谱联用技术可以起到更好的作用,并迎来发展的契机。该综述将目前薄层色谱-质谱的联用形式分为3类,一是接口仪器的间接联用,二是质谱对薄层板的原位检测,三是质谱对薄层分离过程的实时监测,并按此分类对典型的联用形式进行了总结和简要描述。随着薄层色谱-生物自显影技术的广泛使用,薄层色谱与质谱联用的技术方法极大地提高了食品、药用生物活性物质的研发效率。目前,薄层色谱与质谱联用发展的主要瓶颈是“即插即用”型部件的设计和商品化。具有实时监测功能,同时又兼备灵活扫描功能和高通量特点的TLC-MS技术也很令人期待。此外,不同种类TLC-MS解吸-电离技术的对比研究也是有待讨论的应用问题。     

甲醇和乙醇在氩气-实时直接分析质谱中的应用

以氩气代替价格昂贵的氦气作为实时直接分析质谱(DART-MS)的工作气体以降低实验成本。甲醇和乙醇作为作为两种辅助性反应试剂,在Ar-DART-MS分析中充当能量传递的媒介和质子的供体,可以提高Ar-DART-MS的电离效率并扩展其应用范围。通过甲醇和乙醇作为反应性试剂在Ar-DART-MS的背景信号及对样品电离影响的分析,探讨了它们的应用范围,以及在电离过程中存在的一些可能的特征反应。该方法的有效性通过对利血平的分析结果获得。     

原位电离质谱技术在食品质量安全检测中的应用

原位电离质谱技术能够在常压环境下直接分析各种食品样品,无需或仅需极少的食品制备,大大提高了分析效率,已经成为一种重要的食品快速分析方法。本文对原位电离质谱的离子化技术和工作流程进行了介绍,从食品污染物检测、非法添加物筛查、食品真伪鉴别和品质评价等方面出发,综述了该技术在食品质量安全检测中的应用。讨论了其应用于食品分析领域时面临的挑战和未来发展趋势。     

实时直接分析质谱新技术及其应用

由于不需要复杂的样品前处理过程,并具有实时、原位分析等特点,常压敞开式离子化技术成为近年来质谱研究的热点之一.实时直接分析(direct analysis in real time,DART)是近年来出现的一种常压敞开式离子化新技术,在食品安全、环境监测、爆炸物检测以及生物医药等诸多研究领域均有广泛的应用.本文简单介绍了常压敞开式离子化方法的发展,DART的基本原理和研究现状.进而介绍了我国质谱研究人员在基于DART的质谱仪器改进、联用技术以及生物药物等检测分析方面取得的新进展和新成果.     

大气压光电离技术及其应用研究进展

大气压光电离离子源(APPI)是一种新兴的用于液质联用的软电离离子源,它是利用光化学作用将气相中样品电离的离子化技术,该技术促进了质谱技术对弱极性化合物的分析检测。介绍了液相色谱–质谱/质谱联用技术中大气压光电离的基本原理、应用优点,综述了其在定性、定量分析检测中的应用。     

常压电离质谱在脂质精确结构解析中的研究进展

脂类化合物的结构和功能与细胞生理过程密切相关,脂质结构的精确解析对探索脂质的生物学功能起着至关重要的作用。常压电离质谱技术的出现为常压敞开环境条件下的原位、实时、直接、快速生物脂质分析和组学研究提供了重要的手段。随着常压电离质谱技术在脂质分析和脂质组学研究的不断深入,对脂质结构特别是碳碳双键(C‖C)位置的精细解析就显得尤为重要。该文详细阐述了基于Paternò-Büchi反应、环氧化、臭氧诱导解离、紫外光解离的常压电离质谱技术,以及这些技术在脂质C‖C位置精确鉴定及异构体区分的应用,并展望了常压电离质谱在脂质化合物精确结构解析方面的发展趋势。     

食用油甘油三酯质谱分析方法的研究进展

该文对质谱鉴定技术及其与色谱联用的分析方法(包括直接进样质谱分析、气相色谱质谱联用技术、超临界流体与质谱联用技术和液相色谱质谱联用技术)在甘油三酯分析方面的应用进行了综述,评述了各类分析方法的优缺点,对常用的脂质分析数据库进行了介绍,并对甘油三酯分析方法的发展及应用作了展望。     

Rapid direct analysis in real time (DART) mass spectrometric detection of juvenile hormone III and its terpene precursors

Direct analysis in real time (DART) is a plasma-based ambient ionization technique that enables rapid ionization of small molecules with high sample throughput. In this work, DART was coupled to an orthogonal (oa) time-of-flight (TOF) mass spectrometer and the system was optimized for analyzing a vital hormonal regulator in insects, juvenile hormone (JH) III and its terpene precursors, namely, farnesol, farnesoic acid, and methyl farnesoate. Optimization experiments were planned using design of experiments (DOE) full factorial models to identify the most significant DART variables contributing to JH III analysis sensitivity by DART-TOF mass spectrometry (MS). The optimized DART-TOF MS method had femtomole to sub-picomole detection limits for terpene standards, along with mass accuracies below 5 ppm. Finally, the possibility of distinguishing between two farnesol isomers by in-source-collision-induced dissociation (CID) in the first differentially pumped region of the oaTOF mass spectrometer was investigated. DART-MS enabled high-throughput, sensitive analysis with acquisition times ranging from 30 s to a minute. To the best of our knowledge, this is the first report on the application of DART-MS to the detection and identification of volatile or semi-volatile insect terpenoids, and on the use of DOE approaches to optimize DART-MS analytical procedures.     

Direct analysis in real time—a critical review on DART-MS

Direct analysis in real time mass spectrometry (DART-MS) has become an established technique for rapid mass spectral analysis of a large variety of samples. DART-MS is capable of analyzing the sample at atmospheric pressure, essentially in the open laboratory environment. DART-MS can be applied to compounds that have been deposited or adsorbed on to surfaces or that are being desorbed therefrom into the atmosphere. This makes DART-MS suitable and well-known for analysis of ingredients of plant materials, pesticide monitoring on vegetables, forensic and safety applications such as screening for traces of explosives, warfare agents, or illicit drugs on luggage, clothes, or bank notes, etc. DART can also be used for analysis of either solid or liquid bulk materials, as may be required in quality control, or to quickly investigate the identity of a compound from chemical synthesis. Even living organisms can be subjected to DART-MS. Driven by different needs in analytical practice, the combination of the DART ionization source and interface can be configured in multiple geometries and with various accessories to adapt the setup as required. Analysis by DART-MS relies on some sort of gas-phase ionization mechanism. In DART, initial generation of the ionizing species is by use of a corona discharge in a pure helium atmosphere which delivers excited helium atoms that, upon their release into the atmosphere, will initiate a cascade of gas-phase reactions. In the end, this results in reagent ions created from atmospheric water or (solvent) vapor in the vicinity of the surface subject to analysis where they effect a chemical ionization process. DART ionization processes may generate positive or negative ions, predominantly even-electron species, but odd-electron species do also occur. The prevailing process of analyte ion formation from a given sample is highly dependent on analyte properties.     

Quantification of small molecules in plasma with direct analysis in real time tandem mass spectrometry, without sample preparation and liquid chromatographic separation

Recently, a new ion source, Direct Analysis in Real Time (DART), has been introduced which allows direct biological sample introduction into a mass spectrometry (MS) system. The elimination of conventionally required sample preparation and separation by high-performance liquid chromatography (HPLC) prior to MS analysis represents a remarkable opportunity to reduce assay turn-around time, environmental impact and capital/manpower investment. This new technology initially was used in various qualitative applications to directly detect chemicals on solid surfaces, in liquids and gases. In this study, a DART source operating under ambient pressure with ground potential was installed onto a Sciex 4000 tandem mass spectrometer and employed in the sample analysis of plasma based on direct introduction into the DART-MS/MS system. Reasonable precision and accuracy (%CV and %Error, both <10%) were achieved of a significant number of compounds tested in biological fluids. In addition, the limit of detection for 80% of the tested compounds reached 5 ng/mL or lower which is sufficient for pharmaceutical drug discovery support. Finally, experimental conditions that significantly impacted assay performance were investigated with respect to optimization and limitation. Because of its simplicity, fast data acquisition (3-5 s) and low cost, DART has the potential to significantly impact quantitative pharmaceutical analysis in biological matrices.     

Challenging applications offered by direct analysis in real time (DART) in food-quality and safety analysis

Direct analysis in real time (DART) is an ambient ionization technique undergoing rapid development. With minimal sample pre-treatment, ionization of analyte molecules outside the mass spectrometry (MS) instrument in the ordinary atmosphere is feasible. This ionization approach relies upon the fundamental principles of atmospheric pressure chemical ionization.The current review highlights and critically assesses application of DART (and some related desorption/ionization techniques) coupled to various types of MS analyzers for both target and non-target analysis of complex food matrices. Based on existing studies, DART-MS is presented as a simple, high-throughput tool for:

(i)

qualitative confirmation of chemical identity;

(ii)

metabolomic fingerprinting/profiling; and,

(iii)

quantification of low-molecular-weight food components, including some trace organic contaminants.

With regard to regulatory requirements, we mention practical aspects of DART-MS use, as well as performance characteristics that can be attained.     

Rapid screening for synthetic antidiabetic drug adulteration in herbal dietary supplements using direct analysis in real time mass spectrometry

Adulteration of herbal supplements with synthetic drugs is illegal. A rapid and reliable method which utilizes direct analysis in real time mass spectrometry (DART-MS) was developed for the identification of seven synthetic antidiabetic drugs used as adulterants in herbal dietary supplements. The supplement sample was simply extracted with methanol/water by manually shaking several times and directly analyzed using DART-MS. The presence of synthetic drug adulterants was confirmed through the accurate m/z values and MS/MS data obtained via quadruple time of flight mass spectrometry (QTOF MS). Parameters for the DART source were systematically optimized, and the limits of detection (LODs) in herbal supplement matrices were measured. This method was successfully applied to examine five commercial herbal dietary supplements, and two of them proved to be adulterated with metformin without labeling.     

Coupling of planar chromatography with Direct Analysis in Real Time mass spectrometry

Direct Analysis in Real Time mass spectrometry (DART-MS) is an emerging and rapidly developing area of ambient desorption ionization mass spectrometric techniques. Its coupling with planar chromatography is especially promising, as compared to other ambient desorption ionization techniques, because it does not require the use of liquids that may distort the shape of a spot by diffusion effects. In the first publications on TLC/HPTLC-DART-MS, due to the fixed, horizontally aligned supply of the gas flow from the DART ionization source to the MS inlet, the introduction of HPTLC/TLC plates as cut strips was inconvenient for quantitation, and the repeatability was very low due to the manual positioning. Recently a new version of the DART ion source was suggested, which allows adjusting the angle of the DART gas stream and the use of a motorized rail, thereby, improving highly the capabilities of TLC/HPTLC-DART-MS. This comprehensive review describes the development and analytical capabilities of TLC/HPTLC-DART-MS, and the general DART-MS perspectives for surface analysis or imaging MS.      

DART-Orbitrap MS: a novel mass spectrometric approach for the identification of phenolic compounds in propolis

This is the first direct analysis in real-time mass spectrometry (DART-MS) study of propolis and a first study on the analysis of bee products using high-resolution DART-MS (DART-HRMS). Identification of flavonoids and other phenolic compounds in propolis using direct analysis in real-time coupling with Orbitrap mass spectrometry (DART-Orbitrap MS) was performed in the negative ion mode for minimizing the matrix effects, while the positive ion mode was used for the confirmation of selected compounds. Possible elemental formulae were suggested for marker components. The duration of one sample analysis by DART-MS analysis lasted ca. 30 s, and all benefits of high-resolution mass spectrometry were used upon data processing using the coupling of DART with the Orbitrap mass spectrometer. The possibility for scanning analysis of dried propolis extract spots on a planar porous surface was investigated in the heated gas flow of the DART ion source with adjustable angle. As an independent method, the approach of scanning analysis is of high interest and of future potential for confirmation of the results obtained from liquid sample analysis. Scanning analysis is highly promising for further development in the bioanalytical field due to the convenience of the storage and transportation of dried sample spots.     

The coupling of direct analysis in real time ionization to Fourier transform ion cyclotron resonance mass spectrometry for ultrahigh‐resolution mass analysis

Direct Analysis in Real Time (DART) is an ambient ionization technique for mass spectrometry that provides rapid and sensitive analyses with little or no sample preparation. DART has been reported primarily for mass analyzers of low to moderate resolving power such as quadrupole ion traps and time‐of‐flight (TOF) mass spectrometers. In the current work, a custom‐built DART source has been successfully coupled to two different Fourier transform ion cyclotron resonance (FT‐ICR) mass spectrometers for the first time. Comparison of spectra of the isobaric compounds, diisopropyl methylphosphonate and theophylline, acquired by 4.7 T FT‐ICR MS and TOF MS, demonstrates that the TOF resolving power can be insufficient for compositionally complex samples. 9.4 T FT‐ICR MS yielded the highest mass resolving power yet reported with DART ionization for 1,2‐benzanthracene and 9,10‐diphenylanthracene. Polycyclic aromatic hydrocarbons exhibit a spatial dependence in ionization mechanisms between the DART source and the mass spectrometer. The feasibility of analyzing a variety of samples was established with the introduction and analysis of food products and crude oil samples. DART FT‐ICR MS provides complex sample analysis that is rapid, highly selective and information‐rich, but limited to relatively low‐mass analytes. Copyright © 2010 John Wiley & Sons, Ltd.     

Analysis of Geting Bituminous Coal by Electrospray Ionization and Direct Analysis in Real Time Mass Spectrometry

Understanding the structure and composition of coals is important for effective, clean, and value-added utilization. In addition to gas chromatography/mass spectrometry which is commonly used to analyze coal, mass spectrometry (MS) may be used with other ion sources such as electrospray ionization (ESI) and direct analysis in real time (DART) for characterization. In this work, Geting bituminous coal was extracted sequentially and exhaustively with petroleum ether, carbon disulfide, methanol, acetone, an isometric acetone/carbon disulfide mixture, tetrahydrofuran, and an isometric tetrahydrofuran/carbon disulfide mixture. Raw coal, extracts, and the extraction residue were analyzed using MS equipped with ESI or DART. Organic heteroatomic species in the extracts were determined by liquid chromatography-mass spectrometry equipped with ESI. Molecular weight distributions of organic species in raw coal, extracts, and extraction residue were characterized by ESI-MS and DART-MS. Associated molecules and homologous compounds in coal extracts were identified.