Direct desorption/ionization of analytes by microwave plasma torch for ambient mass spectrometric analysis

Ambient ionization is the new revolution in mass spectrometry (MS). A microwave plasma produced by a microwave plasma torch (MPT) at atmospheric pressure was directly used for ambient mass spectrometric analysis. H₃O⁺ and NH₄⁺ and their water clusters from the background are formed and create protonated molecules and ammoniated molecules of the analytes. In the full‐scan mass spectra, both the quasi‐molecular ions of the analytes and their characteristic ionic fragments are obtained and provide evidence of the analyte. The successful detection of active compounds in both medicine and garlic proves that MPT has the efficient desorption/ionization capability to analyze solid samples. The obtained decay curve of nicotine in exhaled breath indicates that MPT‐MS is a useful tool for monitoring gas samples in real time. These results showed that the MPT, with the advantages of stable plasma, minimal optimization, easy, solvent‐free operation, and no pretreatment, is another potential technique for ambient MS. Copyright © 2013 John Wiley & Sons, Ltd.     

An improved microwave plasma torch for atomic spectrometry

The analytical performance of a microwave plasma torch was improved through mechanical alterations. Several problems reported in earlier designs were addressed: the ignition and stabilization of a helium plasma in the MPT was difficult; high powers were required to both ignite and operate the plasma; otherwise, the plasma would erratically change from an annular to a filament type discharge. In the new torch, the helium discharge was stabilized by replacing the copper central tube with one made of quartz. In addition, air entrainment was alleviated through use of a sheathing gas. This modification simplified the background mass spectrum and raised the effective ionization temperature of the discharge. A detailed schematic diagram of the new microwave plasma torch is presented.     

Distinguishing N-oxide and hydroxyl compounds: impact of heated capillary/heated ion transfer tube in inducing atmospheric pressure ionization source decompositions

In the pharmaceutical industry, a higher attrition rate during the drug discovery process means a lower drug failure rate in the later stages. This translates into shorter drug development time and reduced cost for bringing a drug to market. Over the past few years, analytical strategies based on liquid chromatography/mass spectrometry (LC/MS) have gone through revolutionary changes and presently accommodate most of the needs of the pharmaceutical industry. Among these LC/MS techniques, collision induced dissociation (CID) or tandem mass spectrometry (MS/MS and MS(n)) techniques have been widely used to identify unknown compounds and characterize metabolites. MS/MS methods are generally ineffective for distinguishing isomeric compounds such as metabolites involving oxygenation of carbon or nitrogen atoms. Most recently, atmospheric pressure ionization (API) source decomposition methods have been shown to aid in the mass spectral distinction of isomeric oxygenated (N-oxide vs hydroxyl) products/metabolites. In previous studies, experiments were conducted using mass spectrometers equipped with a heated capillary interface between the mass analyzer and the ionization source. In the present study, we investigated the impact of the length of a heated capillary or heated ion transfer tube (a newer version of the heated capillary designed for accommodating orthogonal API source design) in inducing for-API source deoxygenation that allows the distinction of N-oxide from hydroxyl compounds. 8-Hydroxyquinoline (HO-Q), quinoline-N-oxide (Q-NO) and 8-hydroxyquinoline-N-oxide (HO-Q-NO) were used as model compounds on three different mass spectrometers (LCQ Deca, LCQ Advantage and TSQ Quantum). Irrespective of heated capillary or ion transfer tube length, N-oxides from this class of compounds underwent predominantly deoxygenation decomposition under atmospheric pressure chemical ionization conditions and the abundance of the diagnostic [M + H - O](+) ions increased with increasing vaporizer temperature. Furthermore, the results suggest that in API source decompostion methods described in this paper can be conducted using mass spectrometers with non-heated capillary or ion transfer tube API interfaces. Because N-oxides can undergo in-source decomposition and interfere with quantitation experiments, particular attention should be paid when developing API based bioanalytical methods.     

Combining capillary with radio-frequency-only quadrupole as an interface for a home-made time-of-flight mass spectrometer

A heated capillary tube combined with a radio-frequency-only quadrupole has been coupled with a home- made, high-resolution orthogonal-injection, time-of-flight mass spectrometer to improve ion transmission from the atmospheric pressure to the low--pressure regions. With an electrospray ion source, the performance of the interface on the intensity of spectra was investigated. For electrospray ionization, the ion intensity detected on the time-of- flight mass spectrometer was seen to increase three-fold compared with an orifice interface. It has been shown that the enhanced ion inlet designs can not only increase the ion translation efficiency, but also improve the detection limits of the mass spectrometer. Coupling atmospheric pressure matrix-assisted laser desorption/ionization with the improved interface resulted in an instrument detection limit as low as 2.5 fmol.     

Analysis of underivatized amino acid mixtures using high performance liquid chromatography/dual oscillating nebulizer atmospheric pressure microwave induced plasma ionization-mass spectrometry

A dual oscillating capillary nebulizer (OCN) in conjunction with an atmospheric pressure microwave induced plasma ionization (AP-MIPI) source was applied to the analysis of underivatized amino acid mixtures. It was found that, compared to the single OCN, the dual OCN enhanced the sensitivity of detection several fold. Enhanced sensitivity was compound dependent. For small molecules, such as amino acids, it was 2-5 times more sensitive, while for larger molecules such as peptides it was more than an order of magnitude. The increase in sensitivity was attributed to the enhanced nebulization of the new torch. By using water/ acetonitrile containing 0.1% nonafluoropentanoic acid as the high performance liquid chromatography (HPLC) mobile phase and a C18 column, all common amino acids were separated and detected. A comparison between the results obtained using microwave induced plasma, atmospheric pressure chemical ionization (APCI), and electrospray ionization (ESI) at flow rates compatible with micro LC (10-100 microL/min) showed a higher sensitivity of detection with the AP-MIPI technique for the analysis of underivatized amino acids.     

Construction and characterization of a small-bore electrospray ionization source

A simple, economical, and efficient electrospray ionization (ESI) source has been constructed in the configuration of a probe that makes use of a standard 13 mm vacuum lock. The principal components have been placed inside a glass tube making use of the electrical insulating properties of the glass while allowing for visual adjustments to be readily made. The ESI source, a variation of an atmospheric pressure ionization interface, is a modified version of designs published by Chait et al. (Rapid Comm. Mass Spectrom. 1990, 4, 81–87) and Knapp et al. (Anal. Chem. 1991, 63, 1658–1660) wherein a heated metal capillary is used for desolvation. The ESI probe has been tested on three different Extrel quadrupole mass spectrometers, with removable ion volumes, using polypeptides and small proteins. No modifications to the standard electron ionization/chemical ionization lens assembly were required to obtain excellent results other than removal of the ion volume. The spectra acquired were in excellent agreement with those previously published.     

Secondary processes in atmospheric pressure chemical ionization–ion trap mass spectrometry: a case study of orotic acid

Atmospheric pressure chemical ionization is known for producing unusual artifacts of the ionization process in some cases. In this work, processes occuring in atmospheric pressure chemical ionization/MS of orotic acid that afforded ions accompanying protonated and deprotonated orotic acid molecules in the spectra were studied. Two processes ran in parallel in the ion source: decarboxylation of neutral orotic acid and collision‐induced dissociation of its protonated or deprotonated form. A procedure discerning pre‐ionization decomposition and post‐ionization dissociation by manipulating ion source parameters was proposed. Experiments with isotopically labeled solvents confirmed ion–molecule reactions of the product of collision‐induced dissociation of protonated orotic acid with solvent molecules in the ion source and even under vacuum in the ion trap. Copyright © 2012 John Wiley & Sons, Ltd.     

A cylindrical capacitor ionization source: droplet generation and controlled charge reduction for mass spectrometry

A cylindrical capacitor ionization source was used in conjunction with corona discharge charge reduction for generation of singly charged ions for mass spectrometric analysis. The source consists of a fused-silica capillary threaded with a platinum wire and placed inside a stainless steel tube. Application of an electric potential to the wire results in the production of a linear stream of charged droplets when an aqueous solution is pumped through the capillary. Subsequent solvent evaporation yields ions, providing a continuous ion source for mass spectrometry. Passage of the ions through a corona discharge charge reduction chamber permits reduction of the charge state to predominantly singly charged species, facilitating analysis of DNA and protein mixtures. The change from production of multiply charged ions to production of singly charged ions is extremely simple, requiring only modulation of the voltage applied to the corona discharge electrode. A simple technique for construction of the ionization source is reported.     

An evaluation of atmospheric pressure ionization techniques for the analysis of N-Methyl carbamate pesticides by liquid chromatography mass spectrometry

Atmospheric pressure ionization (API) techniques are evaluated for the mass spectral analysis of N-methyl carbamate pesticides. Atmospheric pressure chemical ionization (APCI) using a heated nebulizer interface provided both protonated molecules and abundant, characteristic fragment ions. With ion spray (ISP; pneumatically assisted electrospray ionization), which utilizes a milder “ion evaporation” process, primarily protonated molecules were obtained, although fragment ions similar to those observed in APCI could be induced by variation of the API orifice voltage. Product ion spectra of ISP-derived protonated molecules, generated by tandem mass spectrometry using collision-induced dissociation, are also presented. The APCI and ISP spectra of the carbamates are compared to those obtained with a thermospray interface and also to their electron ionization and methane CI spectra obtained with a particle beam interface. For all four interfaces, combined liquid chromatography mass spectrometry methods using conventional (4.6 mm i.d.) columns are described for the separation and detection of pesticide mixtures. These methods are applied to the confirmatory analysis of three representative carbamate pesticides, spiked at the 0.1-ppm level in green peppers. For those carbamates amenable to gas chromatography mass spectrometry, comparative results are presented.     

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.     

Aerosol Matrix-Assisted Laser Desorption Ionization Mass Spectrometry

A new method of liquid sample introduction for a time-of-flight mass spectrometer (TOF-MS) has been developed by applying the method of matrix-assisted laser desorption ionization to aerosols. Analyte biomolecules are dissolved in a methanol solvent along with a UVabsorbing matrix and formed into an aerosol with a pneumatic nebulizer. The aerosol particles are dried in a heated skimmer tube before ionization by pulsed 355-nm UV laser radiation. Mass analysis is achieved in a linear TOF-MS. Results for the ionization of bovine insulin (5733.5 Mw) are reported.     

A versatile new torch for inductively coupled plasma spectrometry

A modified torch for optical emission spectrometry with an inductively coupled plasma source is described. The demountable torch incorporates a flared intermediate tube, a capillary injector tube and interchangeable jets at the gas inlets. The optimised performance of the torch is compared with that of a conventional torch. The new torch can be operated over a wide range of gas flows and shows considerable promise in work with an argon-cooled plasma. The ability to operate at high or low gas flow rates, and the possibility of interchanging tubes and jets easily illustrate the versatility of the new design.     

Electrospray ionization for determination of non‐polar polyaromatic hydrocarbons and polyaromatic heterocycles in heavy crude oil asphaltenes

Electrospray ionization (ESI) is the most common ionization method in atmospheric pressure ionization mass spectrometry because of its easy use and handling and because a diverse range of components can be effectively ionized from high to medium polarity. Usually, ESI is not employed for the analysis of non‐polar hydrocarbons, but under some circumstances, they are effectively ionized. Polyaromatic hydrocarbons and aromatic heterocycles can form radical ions and protonated molecules after ESI, which were detected by Fourier transform ion cyclotron resonance mass spectrometry. The highly condensed aromatic structures are obtained from a heavy crude oil, and the results show class distribution from pure hydrocarbons up to more non‐basic nitrogen‐containing species. By using different solvent compositions [toluene/methanol (50/50 v/v), dichloromethane/methanol (50/50 v/v), dichloromethane/acetonitrile (50/50 v/v) and chloroform], the results show that the lack of proton donor agent helps to preserve the radical formation that was created at the metal/solution interface inside the electrospray capillary. The results demonstrate that with an appropriate selection of solvent and capillary voltage, the ratio between the detected radical ion and protonated molecule form can be manipulated. Therefore, ESI can be expanded for the investigation of asphaltene and other polyaromatic systems beyond the polar constituents as non‐polar hydrocarbons can be efficiently analyzed. Copyright © 2015 John Wiley & Sons, Ltd.     

Laser spray: electric field-assisted matrix-assisted laser desorption/ionization

A new liquid chromatography/mass spectrometry interface, the laser spray, has been developed. Explosive vaporization and mist formation occur when an aqueous solution effusing out from the tip of the stainless-steel capillary is irradiated from the opposite side of the capillary by a 10.6 microm infrared laser. Weak ion signals could be detected when the plume was sampled through the ion sampling orifice. When a high voltage (3-4 kV) was applied to the stainless-steel capillary, strong ion signals appeared. The ion abundances were found to be orders of magnitude greater than those obtained by conventional electrospray ionization in the case of aqueous solutions. The present method is regarded as an electric-field assisted form of matrix-assisted laser desorption/ionization in which the liquid chromatographic solvent (water, etc.) acts as a liquid matrix. Laser spray ionization is expected to become a versatile method for biological mass spectrometry because this method is compatible with the natural solvent, water.     

Modified helium pulse-operated microwave induced plasma for spectrochemical analysis of liquid samples

To minimize problems caused by sample introduction into helium pulse operated microwave-induced plasma (He-pulsed-MIP), a simple plasma torch was developed. This torch is constructed from commonly available components with an absolute minimum of machining. In this torch, plasma is kept operating by partially isolating it from the rest of the plasma (within the plasma chamber). This auxiliary plasma is by-passed during sample or solvent injection and is therefore not affected. The design of this discharge chamber was thoroughly examined and each parameter affecting its analytical performance was evaluated. Measurements reported include effect of helium flow rate, discharge tube position and microwave power on analytical performance. Analytical calibration curves and detection limits data are shown for Ca, Cd, Cr, Cu, Fe, Mg, Ni and Zn. Plasma excitation temperature was determined using iron and copper as thermometric species. Finally, the present technique was applied to the analysis of real biological samples (liver, brain, heart, bone, kidney, tests, serum, spleen and muscles of white albino rats). The results were compared with those obtained using flame atomic absorption spectroscopy.     

Reviews on recent trends in chromatography/mass spectrometry coupling. Part IV. Reasons why supercritical fluid chromatography is not so easily coupled with mass spectrometry as originally assessed

Summary When SFC was rediscovered in the early 1980s, it was frequently estimated that a strong driving force to its development would be the ease of devising a simple SFC/MS interface. This was believed to be easily achieved if analytical conditions were limited to capillary SFC columns as a general separation tool, and to the choice of neat CO₂ as the unique supercritical fluid. The low flow rate of mobile phase delivered by capillary columns was easy to accommodate by the vacuum equipment of standard mass spectrometers, and the specific physical properties of CO₂ made possible solute ionization by different ion-molecule reactions, especially charge exchange ionization. This approach has lived up to all of its promises. The major causes of the observed mismatch are the large variations of the MS source pressure as a result of the CO₂ pressure gradient at the SFC column inlet, the low sensitivity of charge exchange ionization at these high MS source pressures, and the inability to handle polar and nonvolatile molecules. Adaptation of LC/MS interfaces, such as the thermospray interface or the particle beam interface, to SFC/MS conditions was a step forward, but these devices have their own limitations. Alternative methods to direct SFC/MS coupling have been investigated recently. They are based on the use of packed columns rather than capillaries, and on solute ionization at atmospheric pressure rather than under a vacuum, by means of either gas-phase corona discharge ionization or liquidphase electrospray ionization. These new developments may revive research into the design of reproducible and sensitive SFC/MS systems where the number of recent studies is still low compared with other chromatography/mass spectrometry coupling studies.See [1] for part III     

Gas-phase proton transfer reactions involving multiply charged cytochrome c ions and water under thermal conditions

Investigations of gas-phase proton transfer reactions have been performed on protein molecular ions generated by electrospray ionization (ESI). Their reactions were studied in a heated capillary inlet/reactor prior to expansion into a quadrupole mass spectrometer. Results from investigations involving protonated horse heart cytochrome c and H, O suggest that Coulombit effects can lower reaction barriers as well as aid in entropically driven reactions. For example, the charge state distribution observed by a quadrupole mass spectrometer for multiply protonated cytochrome c without the addition of any reactive gas ranges from 9+ to 19+ , with the [M + 15H]¹⁵⁺ ion being the most intense peak. With the addition of H₂O (proton affinity approximately 170.3±2 kcal/mol) to the capillary reactor at 120°C, the charge state distribution shifts to a lower charge, ranging from 13+ to less than 9+. Under the same conditions with argon (proton affinity approximately 100 kcal/mol) as the reactive gas, no shift in the charge state distribution is observed. The results demonstrate that proton transfer to water can occur for highly protonated molecular ions, a process that would be expected to be highly endothermic for singly protonated molecules (for which Coulombic destabilization is not significant). The results imply that the charge state distribution from ESI is somewhat dependent upon the mechanism and speed of the droplet evaporation/ion desolvation process, which may vary substantially with the ESI/mass spectrometry interface design.     

Aliphatic Hydrocarbon Spectra by Helium Ionization Mass Spectrometry (HIMS) on a Modified Atmospheric-Pressure Source Designed for Electrospray Ionization

Chemical-ionization techniques that use metastable species to ionize analytes traditionally use a flat pin or a sharp solid needle onto which the high potential needed to generate the discharge plasma is applied. We report here that direct analysis of samples containing volatile and semivolatile compounds, including saturated and unsaturated aliphatic hydrocarbons, can be achieved on any electrospray-ionization mass spectrometer by passing helium though the sample delivery metal capillary held at a high potential. In the helium plasma ionization source (HPIS) described here, the typical helium flow required (about 20–30 mL/min), was significantly lower than that needed for other helium-ionization sources. By this procedure, positive ions were generated by nominal hydride ion removal from molecules emanating from heated saturated hydrocarbons as large as tetratetracontane (C₄₄H₉₀), at capillary voltages ranging from 2.0 to 4.0 kV. Unsaturated hydrocarbons, on the other hand, underwent facile protonation under much lower capillary voltages (0.9 to 2.0 kV). Although saturated and monounsaturated hydrocarbons bearing the same number of carbon atoms generate ions of the same m/z ratio, a gas-phase deuterium exchange method is described to ascertain the identity of these isomeric ions originating from either protonation or hydride abstraction mechanisms. Moreover, mass spectrometric results obtained by exposing unsaturated hydrocarbons to D₂O vapor in an HPIS-MS instrument confirmed that the proton donor for ionization of unsaturated hydrocarbons is protonated water.     

Modified helium pulse-operated microwave induced plasma for spectrochemical analysis of liquid samples

To minimize problems caused by sample introduction into helium pulse operated microwave-induced plasma (He-pulsed-MIP), a simple plasma torch was developed. This torch is constructed from commonly available components with an absolute minimum of machining. In this torch, plasma is kept operating by partially isolating it from the rest of the plasma (within the plasma chamber). This auxiliary plasma is by-passed during sample or solvent injection and is therefore not affected. The design of this discharge chamber was thoroughly examined and each parameter affecting its analytical performance was evaluated. Measurements reported include effect of helium flow rate, discharge tube position and microwave power on analytical performance. Analytical calibration curves and detection limits data are shown for Ca, Cd, Cr, Cu, Fe, Mg, Ni and Zn. Plasma excitation temperature was determined using iron and copper as thermometric species. Finally, the present technique was applied to the analysis of real biological samples (liver, brain, heart, bone, kidney, tests, serum, spleen and muscles of white albino rats). The results were compared with those obtained using flame atomic absorption spectroscopy. Received: 3 February 2000 / Revised: 16 May 2000 / Accepted: 22 May 2000     

Thermal desorption counter‐flow introduction atmospheric pressure chemical ionization for direct mass spectrometry of ecstasy tablets

A novel approach to the analysis of ecstasy tablets by direct mass spectrometry coupled with thermal desorption (TD) and counter‐flow introduction atmospheric pressure chemical ionization (CFI‐APCI) is described. Analytes were thermally desorbed with a metal block heater and introduced to a CFI‐APCI source with ambient air by a diaphragm pump. Water in the air was sufficient to act as the reactive reagent responsible for the generation of ions in the positive corona discharge. TD‐CFI‐APCI required neither a nebulizing gas nor solvent flow and the accompanying laborious optimizations. Ions generated were sent in the direction opposite to the air flow by an electric field and introduced into an ion trap mass spectrometer. The major ions corresponding to the protonated molecules ([M + H]⁺) were observed with several fragment ions in full scan mass spectrometry (MS) mode. Collision‐induced dissociation of protonated molecules gave characteristic product‐ion mass spectra and provided identification of the analytes within 5 s. The method required neither sample pretreatment nor a chromatographic separation step. The effectiveness of the combination of TD and CFI‐APCI was demonstrated by application to the direct mass spectrometric analysis of ecstasy tablets and legal pharmaceutical products. Copyright © 2009 John Wiley & Sons, Ltd.