Established and emerging atmospheric pressure surface sampling/ionization techniques for mass spectrometry

The number and type of atmospheric pressure techniques suitable for sampling analytes from surfaces, forming ions from these analytes, and subsequently transporting these ions into vacuum for interrogation by MS have rapidly expanded over the last several years. Moreover, the literature in this area is complicated by an explosion in acronyms for these techniques, many of which provide no information relating to the chemical or physical processes involved. In this tutorial article, we sort this vast array of techniques into relatively few categories on the basis of the approaches used for surface sampling and ionization. For each technique, we explain, as best known, many of the underlying principles of operation, describe representative applications, and in some cases, discuss needed research or advancements and attempt to forecast their future analytical utility. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Ambient ionization mass spectrometry: a tutorial

Ambient ionization is a set of mass spectrometric ionization techniques performed under ambient conditions that allows the direct analysis of sample surfaces with little or no sample pretreatment. Using combinations of different types of sample introduction systems and ionization methods, several novel techniques have been developed over the last few years with many applications (e.g., food safety screening; detection of pharmaceuticals and drug abuse; monitoring of environmental pollutants; detection of explosives for antiterrorism and forensics; characterization of biological compounds for proteomics and metabolomics; molecular imaging analysis; and monitoring chemical and biochemical reactions). Electrospray ionization and atmospheric pressure chemical ionization are the two main ionization principles most commonly used in ambient ionization mass spectrometry. This tutorial paper provides a review of the publications related to ambient ionization techniques. We describe and compare the underlying principles of operation, ionization processes, detecting mass ranges, sensitivity, and representative applications of these techniques.     

Laser desorption-atmospheric pressure chemical ionization: a novel ion source for the direct coupling of polyacrylamide gel electrophoresis to mass spectrometry

Laser desorption-atmospheric pressure chemical ionization-mass spectrometry (LD-APCI-MS) is presented for the atmospheric pressure (AP) sampling of tryptic peptides directly from a polyacrylamide gel. In contrast to other gel sampling mass spectrometric approaches, this technique does not require the addition of any exogenous matrices to the gel to assist with ionization. In this arrangement, a CO(2) laser at 10.6 micro m is used to desorb intact neutral peptide molecules from the gel, followed by ionization in the gas-phase with APCI. The ions are then sampled via a heated capillary inlet and transferred to a quadrupole ion trap mass spectrometer for mass analysis. Preliminary results suggest the polyacrylamide gel electrophoresis-LD-APCI-MS technique provides several advantages that could translate into a more convenient, robust methodology for the rapid identification and characterization of proteins. Finally, strategies regarding the further development of the method are presented.     

Comparison of the sensitivity of mass spectrometry atmospheric pressure ionization techniques in the analysis of porphyrinoids

The porphyrinoids chemistry is greatly dependent on the data obtained in mass spectrometry. For this reason, it is essential to determine the range of applicability of mass spectrometry ionization methods. In this study, the sensitivity of three different atmospheric pressure ionization techniques, electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization, was tested for several porphyrinods and their metallocomplexes. Electrospray ionization method was shown to be the best ionization technique because of its high sensitivity for derivatives of cyanocobalamin, free‐base corroles and porphyrins. In the case of metallocorroles and metalloporphyrins, atmospheric pressure photoionization with dopant proved to be the most sensitive ionization method. It was also shown that for relatively acidic compounds, particularly for corroles, the negative ion mode provides better sensitivity than the positive ion mode. The results supply a lot of relevant information on the methodology of porphyrinoids analysis carried out by mass spectrometry. The information can be useful in designing future MS or liquid chromatography–MS experiments. Copyright © 2013 John Wiley & Sons, Ltd.     

Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates

We report the evaluation of several mass spectrometry‐based methods for the determination of carisoprodol and meprobamate in samples obtained from the rat brain by in vivo intracranial microdialyis. Among the techniques that aspire to perform analyses without chromatographic separation and thereby increase throughput, chip‐based nanoelectrospray ionization and the use of an atmospheric pressure solids analysis probe fell short of requirements because of insufficient detection sensitivity and hard ionization, respectively. Although direct analysis in real time provided the required soft ionization, shortcomings of a tandem mass spectrometry‐based assay also included inadequate detection sensitivity and, in addition, poor quantitative reproducibility. Therefore, liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry was developed to determine carisoprodol and meprobamate from artificial cerebrospinal fluid as the medium. No desalting and/or extraction of the samples was necessary. The assay, combined with in vivo sampling via intracranial microdialyis, afforded time‐resolved concentration profiles for the drug and its major metabolite from the nucleus accumbens region of the brain in rats after systemic administration of carisoprodol. Copyright © 2016 John Wiley & Sons, Ltd.     

Surface desorption atmospheric pressure chemical ionization mass spectrometry for direct ambient sample analysis without toxic chemical contamination

Ambient mass spectrometry, pioneered with desorption electrospray ionization (DESI) technique, is of increasing interest in recent years. In this study, a corona discharge ionization source is adapted for direct surface desorption chemical ionization of compounds on various surfaces at atmospheric pressure. Ambient air, with about 60% relative humidity, is used as a reagent to generate primary ions such as H(3)O(+), which is then directed to impact the sample surface for desorption and ionization. Under experimental conditions, protonated or deprotonated molecules of analytes present on various samples are observed using positive or negative corona discharge. Fast detection of trace amounts of analytes present in pharmaceutical preparations, viz foods, skins and clothes has been demonstrated without any sample pretreatment. Taking the advantage of the gasless setup, powder samples such as amino acids and mixtures of pharmaceutical preparations are rapidly analyzed. Impurities such as sudan dyes in tomato sauce are detected semiquantitatively. Molecular markers (e.g. putrescine) for meat spoilage are successfully identified from an artificially spoiled fish sample. Chemical warfare agent stimulants, explosives and herbicides are directly detected from the skin samples and clothing exposed to these compounds. This provides a detection limit of sub-pg (S/N > or = 3) range in MS2. Metabolites and consumed chemicals such as glucose are detected successfully from human skins. Conclusively, surface desorption atmospheric pressure chemical ionization (DAPCI) mass spectrometry, without toxic chemical contamination, detects various compounds in complex matrices, showing promising applications for analyses of human related samples.     

Assessment of the various ionization methods in the analysis of metal salen complexes by mass spectrometry

Metal salen complexes are one of the most frequently used catalysts in enantioselective organic synthesis. In the present work, we compare a series of ionization methods that can be used for the mass spectral analysis of two types of metalosalens: ionic complexes (abbreviated as Com⁺X^?) and neutral complexes (NCom). These methods include electron ionization and field desorption (FD) which can be applied to pure samples and atmospheric pressure ionization techniques: electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) which are suitable for solutions. We found that FD is a method of choice for recording molecular ions of the complexes containing even loosely bonded ligands. The results obtained using atmospheric pressure ionization methods show that the results depend mainly on the structure of metal salen complex and the ionization method. In ESI spectra, Com⁺ ions were observed, while in APCI and APPI spectra both Com⁺ and [Com + H]⁺ ions are observed in the ratio depending on the structure of the metal salen complex and the solvent used in the analysis. For complexes with tetrafluoroborate counterion, an elimination of BF₃ took place, and ions corresponding to complexes with fluoride counterion were observed. Experiments comparing the relative sensitivity of ESI, APCI and APPI (with and without a dopant) methods showed that for the majority of the studied complexes ESI is the most sensitive one; however, the sensitivity of APCI is usually less than two times lower and for some compounds is even higher than the sensitivity of ESI. Both methods show very high linearity of the calibration curve in a range of about 3 orders of magnitude of the sample concentration. Copyright © 2014 John Wiley & Sons, Ltd.     

Development of medium pressure laser ionization,MPLI. Description of the MPLI ion source

A novel pulsed valve/ion source combination capable of time-resolved sampling from atmospheric pressure has been developed for use with laser ionization time of flight mass spectrometry. The source allows ionization extremely close to the nozzle of the pulsed valve, enabling ultra-sensitive detection of a number of compounds, e.g., NO, at mixing ratios <1 pptV. Furthermore, at analyte mixing ratios in the ppbV range, the temporal resolution of the system is in the sub-second regime, allowing time-resolved monitoring of highly dynamic and complex mixtures, e.g., human breath or reacting chemical mixtures in atmospheric smog chamber experiments. Rotational temperatures of approximately 50 K have been observed for analytes seeded in the supersonic jet expansion at a distance of 1 mm downstream of the nozzle orifice. The refinement of the original ion source has drastically reduced the impact of reflected laser light and the resultant electron impact signals previously observed. The general applicability of this technique is demonstrated here by coupling the source to commercially available as well as home-built time-of-flight mass spectrometers. Finally, we discuss the MPLI technique in view of the very recently introduced atmospheric pressure laser ionization (APLI) as well as the traditional jet-REMPI approach.     

Direct probe CI-MS and APCI-MS for direct materials analysis

Direct probe in vacuo chemical ionization (isobutane CI-MS) and Pyroprobe atmospheric pressure chemical ionization (APCI-MS) are complementary techniques for the analysis of polymeric materials. Both techniques can generally be used to detect residual chemicals and more volatile additives (via thermal desorption), as well as polymeric components (via pyrolysis).Isobutane CI-MS is often a “softer” technique than APCI-MS, giving less background, less fragmentation, and more predictable and reproducible spectra. APCI, on the other hand, provides a higher maximum temperature and a means to carry out sample heating at atmospheric pressure (to simulate TGA). Pyroprobe APCI with high performance instruments has the added features of high resolution mass measurement (to determine atomic compositions) and tandem mass spectrometry (MS/MS, to obtain fragmentation patterns).     

Nebulization ionization and desorption ionization analysis of reactive organofunctionalized silanes in nanofilm products

Three different and recently developed desorption ionization techniques, transmission-mode desorption electrospray ionization (TM-DESI), low temperature plasma (LTP) ionization and nano-assisted laser desorption ionization (NALDI), are compared with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) for the analysis of two nanofilm products (NFPs) for surface coating, which contain hydrolysates and condensates of organo-functionalized silanes. The NFPs were characterized in different states from the liquid phase to the fully formed surface film. The LTP spectra were dominated by the silanes, while the corresponding di-, tri- and tetrasiloxanes were common in ESI, APCI and TM-DESI. This indicates readily condensation of the silanes during the ESI and APCI ionization processes leading to the observed siloxanes. NALDI showed larger siloxane structures than the other techniques, indicating film formation on the NALDI target. Real-time monitoring of the film formation on a glass surface by LTP showed a decreasing abundance of the silanes, while the abundances of the di-, tri and tetrasiloxanes increased significantly within the first 100 s. LTP was superior in showing the non-reacted content of the NFPs, while ESI, APCI and TM-DESI were characterized by artefact formation of siloxanes. NALDI was ideal for showing the siloxane structures of the formed film. The applicabilities of each of the ionization techniques were examined, showing the advantage of utilizing more than one ionization technique for the analysis of reactive species.     

Toward Depth-Resolved Analysis of Plant Metabolites by Nanospray Desorption Electrospray Ionization Mass Spectrometry

Nanospray desorption electrospray ionization (nano-DESI) is one of the ambient desorption ionization methods for mass spectrometry (MS), and it utilizes a steady-state liquid junction formed between two microcapillaries to directly extract analytes from sample surfaces with minimal sample damage. In this study, we employed nano-DESI MS to perform a metabolite fingerprinting analysis directly from a Hypericum leaf surface. Moreover, we investigated whether changes in metabolite fingerprints with time can be related to metabolite distribution according to depth. From a raw Hypericum leaf, the mass spectral fingerprints of key metabolites, including flavonoids and prenylated phloroglucinols, were successfully obtained using ethanol as a nano-DESI solvent, and the changes in their intensities were observed with time via full mass scan experiments. In addition, the differential extraction patterns of the obtained mass spectral fingerprints were clearly visualized over time through selected ion monitoring and pseudo-selected reaction monitoring experiments. To examine the correlation between the time-dependent changes in the metabolite fingerprints and depth-wise metabolite distribution, we performed a nano-DESI MS analysis against leaves whose surface layers were removed multiple times by forming polymeric gum Arabic films on their surfaces, followed by detaching. The preliminary results showed that the changes in the metabolite fingerprints according to the number of peelings showed a similar pattern with those obtained from the raw leaves over time.     

Analysis of amphetamines and fentanyls by atmospheric pressure desorption/ionization on silicon mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry and its application to forensic analysis of drug seizures

The suitability of atmospheric pressure desorption/ionization on silicon mass spectrometry (AP-DIOS-MS) and matrix-assisted laser desorption ionization mass spectrometry (AP-MALDI-MS) for the identification of amphetamines and fentanyls in forensic samples was studied. With both ionization techniques, the mass spectra recorded showed abundant protonated molecules, and the background did not disturb the analysis. The use of tandem mass spectrometry (MS/MS) allowed unambiguous identification of the amphetamines and fentanyls. AP-DIOS-MS/MS and AP-MALDI-MS/MS were also successfully applied to the identification of authentic compounds from drug seizures. Common diluents and tablet materials did not disturb the analysis and compounds were unequivocally identified. The limits of detection (LODs) for amphetamines and fentanyls with AP-DIOS-MS/MS were 1-3 pmol, indicating excellent sensitivity of the method. The LODs with AP-MALDI-MS/MS were about 5-10 times higher.     

表面解吸常压化学电离质谱法直接测定火锅底料中的痕量可卡因

采用表面解吸常压化学电离(SDAPCI)质谱法, 在无需样品预处理情况下, 直接测定了火锅底料中可卡因的含量. 采用取样针取样, 单次取样量在纳升级, 单个样品测定时间少于0.5 min, 回收率为92.9%～106.6%; 相对标准偏差(RSD)为4.7%～11.6%; 可卡因的检出限可达1.5×10-12 g/mL. 该方法适用于批量火锅底料等食品类样品的快速半定量检测.     

Analysis of lipids with desorption atmospheric pressure photoionization‐mass spectrometry (DAPPI‐MS) and desorption electrospray ionization‐mass spectrometry (DESI‐MS)

In this article, the effect of spray solvent on the analysis of selected lipids including fatty acids, fat‐soluble vitamins, triacylglycerols, steroids, phospholipids, and sphingolipids has been studied by two different ambient mass spectrometry (MS) methods, desorption electrospray ionization‐MS (DESI‐MS) and desorption atmospheric pressure photoionization‐MS (DAPPI‐MS). The ionization of the lipids with DESI and DAPPI was strongly dependent on the spray solvent. In most cases, the lipids were detected as protonated or deprotonated molecules; however, other ions were also formed, such as adduct ions (in DESI), [M‐H]⁺ ions (in DESI and DAPPI), radical ions (in DAPPI), and abundant oxidation products (in DESI and DAPPI). DAPPI provided efficient desorption and ionization for neutral and less polar as well as for ionic lipids but caused extensive fragmentation for larger and more labile compounds because of a thermal desorption process. DESI was more suitable for the analysis of the large and labile lipids, but the ionization efficiency for less polar lipids was poor. Both methods were successfully applied to the direct analysis of lipids from pharmaceutical and food products. Although DESI and DAPPI provide efficient analysis of lipids, the multiple and largely unpredictable ionization reactions may set challenges for routine lipid analysis with these methods. Copyright © 2012 John Wiley & Sons, Ltd.     

Atmospheric pressure photoionization for coupling liquid-chromatography to mass spectrometry: A review

This review presents the state-of-the-art techniques that couple liquid chromatography (LC) and mass spectrometry (MS) via atmospheric pressure photoionization (APPI). The different ionization mechanisms are discussed as well as the influence of the mobile phase composition, the nature of the dopant, etc. A comparison with other ionization sources, such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), is reported, and the combination of APPI with these sources is also discussed. Several applications, covering the time period of 2005-2008, for the analysis of drugs, lipids, natural compounds, pesticides, synthetic organics, petroleum derivatives, and other substances are presented.     

Multiphoton ionization spectroscopy in surface analysis and laser desorption mass spectrometry

The application of resonance-enhanced multiphoton ionization (REMPI) spectroscopy for the ultrasensitive detection of molecules originating from laser desorption experiments performed on a variety of substrates is reviewed. Laser-induced desorption from surfaces is capable of producing intact gas-phase molecules, even from polar, non-volatile, high-molecular-weight and thermally labile substances. REMPI is a highly efficient and optically selective ionization method, which, coupled with laser desorption allows the direct chemical analysis of complex mixtures, without the need for previous sample purification and separation steps. The use of REMPI spectroscopy is discussed in two contexts: (1) for the direct chemical analysis of complex mixtures, e.g., environmental samples, by laser desorption/laser postionization mass spectrometry and (2) for measurements of internal state distribution of molecules laser-desorbed from sub-monolayers surface films to gain insight into the laser desorption mechanism.Presented at the 13th International Symposium on Microchemical Techniques (ISM), held in Montreux, Switzerland, May 16–20,1994     

Super‐atmospheric pressure ionization mass spectrometry and its application to ultrafast online protein digestion analysis

Ion source pressure plays a significant role in the process of ionization and the subsequent ion transmission inside a mass spectrometer. Pressurizing the ion source to a gas pressure greater than atmospheric pressure is a relatively new approach that aims to further improve the performance of atmospheric pressure ionization sources. For example, under a super‐atmospheric pressure environment, a stable electrospray can be sustained for liquid with high surface tension such as pure water, because of the suppression of electric discharge. Even for nano‐electrospray ionization (nano‐ESI), which is known to work with aqueous solution, its stability and sensitivity can also be enhanced, particularly in the negative mode when the ion source is pressurized. A brief review on the development of super‐atmospheric pressure ion sources, including high‐pressure electrospray, field desorption and superheated ESI, and the strategies to interface these ion sources to a mass spectrometer will be given. Using a recent ESI prototype with an operating temperature at 220 °C under 27 atm, we also demonstrate that it is possible to achieve an online Asp‐specific protein digestion analysis in which the whole processes of digestion, ionization and MS acquisition could be completed on the order of a few seconds. This method is fast, and the reaction can even be monitored on a near‐real‐time basis. Copyright © 2016 John Wiley & Sons, Ltd.     

Recent advances of ambient ionization mass spectrometry imaging in clinical research

The structural information and spatial distribution of molecules in biological tissues are closely related to the potential molecular mechanisms of disease origin, transfer, and classification. Ambient ionization mass spectrometry imaging is an effective tool that provides molecular images while describing in situ information of biomolecules in complex samples, in which ionization occurs at atmospheric pressure with the samples being analyzed in the native state. Ambient ionization mass spectrometry imaging can directly analyze tissue samples at a fairly high resolution to obtain molecules in situ information on the tissue surface to identify pathological features associated with a disease, resulting in the wide applications in pharmacy, food science, botanical research, and especially clinical research. Herein, novel ambient ionization techniques, such as techniques based on spray and solid‐liquid extraction, techniques based on plasma desorption, techniques based on laser desorption ablation, and techniques based on acoustic desorption were introduced, and the data processing of ambient ionization mass spectrometry imaging was briefly reviewed. Besides, we also highlight recent applications of this imaging technology in clinical researches and discuss the challenges in this imaging technology and the perspectives on the future of the clinical research.     

Application of atmospheric pressure ionization HPLC-MS-MS for the analysis of natural products

Summary The development of techniques utilizing atmospheric pressure ionization, namely atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI), has pioneered the coupling of liquid chromatography (HPLC) with mass spectrometry in recent years. Both ESI and APCI generate ions from polar and labile biomaterials with remarkable ease and efficiency. In particular, the use of HPLC with tandem mass spectrometry (MS-MS) opens further dimensions in the field of bioorganic analysis. Thus, HPLC-MS-MS provides the tools for direct elucidation of the structure and variety of polar natural compounds in complex matrices. In order to develop efficient and straightforward strategies for the analysis of polar natural products, the potential and the limitations of these hyphenated analytical techniques are discussed using heterocyclic aromatic amines, fumonisins, acylated glycoconjugates and regioisomeric fatty acid hydroperoxides as examples. Presented at the 21^st ISC held in Stuttgart, Germany, 15^th–20^th September, 1996     

微波等离子体常压解吸电离质谱法快速检测化学药剂中的活性成分

构建了一种新型电离源--微波等离子体常压解吸电离源, 等离子体由微波等离子体炬产生, 工作气体为Ar气, 微波频率为2450 MHz, 该离子源可在大气压下产生稳定的等离子体. 将该电离源与具有大气压接口的Corsair API-TOF型飞行时间质谱仪结合, 实现了化学药剂中单一或多种主要活性成分的快速分析, 在手动进样条件下, 检测速度可达每小时360次. 在微波等离子体环境下, 活性物质成盐时母体化合物上结合的酸性物质可被直接除掉, 谱图中主要离子为母体化合物的准分子离子[M+H]⁺, 便于识别. 微波等离子体常压解吸电离质谱法无需化学试剂, 具有实时、 快速及无污染等特点, 为药剂研发及化学工业提供了一种新的检测技术.