A dopant for improved sensitivity in easy ambient sonic‐spray ionization mass spectrometry

Recently, 3‐nitrobenzonitrile (3‐NBN) has been used to improve sensitivity of sonic‐spray ionization mass spectrometry. Easy ambient sonic‐spray ionization (EASI) is one of the simplest, gentlest and most used spray‐based desorption/ionization ambient techniques, but limited sensitivity has been commonly taken as its major drawback. Herein we investigate the use of 3‐NBN as a dopant in EASI‐MS for improved sensitivity. Using a few typical EASI samples as test cases, the presence of 10 ppm (µg ml^?1) of 3‐NBN in the spray solvent showed two to fourfold gains in EASI‐MS sensitivity as measured both by total ion current and S/N ratios, accompanied with significant reductions in chemical noise. Sensitivity for DESI using 3‐NBN as a dopant also improved and dopant DESI versus dopant EASI sensitivities were compared. The use of solvent dopants seems therefore to be a promising strategy to improve sensitivity for spray‐based ambient MS techniques. Copyright © 2015 John Wiley & Sons, Ltd.     

Fabric softeners: nearly instantaneous characterization and quality control of cationic surfactants by easy ambient sonic‐spray ionization mass spectrometry

A tiny droplet of typical samples of fabric softeners from different commercial brands placed on a smooth paper surface was subjected to easy ambient sonic‐spray ionization mass spectrometry (EASI‐MS). With no need for sample‐preparation or pre‐separation procedures, EASI‐MS and EASI‐MS/MS identify nearly instantaneously the main surfactants and the homologous series employed in their formulations. Adulterated and low quality samples containing no or less efficient softeners are also easily recognized. Copyright © 2009 John Wiley & Sons, Ltd.     

Salicylaldehyde azine cluster formation observed by cold‐spray ionization mass spectrometry

We installed a cold‐spray ionization (CSI) source on a mass spectrometer to investigate the self‐assembly behavior of an aggregation‐induced emission enhancement system. Using a CSI source and the three‐dimensional platform, a self‐assembly system of a salicylaldehyde azine (SAA) was studied in mixture solution. This method permitted the determination of the structural information of the solution state, which cannot be detected by conventional mass spectrometry. In addition to the [M+H]⁺ ion (M is the SAA molecule), many major ion clusters such as [2M+Na]⁺ at m/z 503, [3M+Na]⁺ at m/z 743, [4M+Na]⁺ at m/z 983 and higher order aggregates were observed in the CSI mass spectra. However, many fragment ions, with the exception of cluster ions, appeared with high abundance when the ESI ion source was used due to the desolvation chamber temperature, suggesting that some aggregation can be detected at low temperatures. To investigate the effect of solvent on the aggregation, the CSI‐mass spectrometry (MS) experiments of SAA in absolute ethanol solution and ethanol/water (good/poor solvent) mixture solution were conducted. The most abundant ion peak was protonated SAA (m/z 241) in absolute ethanol, but many cluster ions and some multiple charged ion peaks were observed after adding a small amount of water into the ethanol solution. The results showed good agreement with that inferred by the combinational analysis of scanning electron microscope and fluorescence microscopy, indicating that CSI‐MS is capable of providing self‐assembly information of labile molecules in the solution state. Copyright © 2013 John Wiley & Sons, Ltd.     

Characterization of an improved thermal ionization cavity source for mass spectrometry

A new thermal ionization source for use with a quadrupole mass spectrometer has been designed and characterized. The new source provides significant advantages over the previously reported prototype source and traditional filament-type thermal ionization sources. The operational interface between the source and the quadrupole mass spectrometer has been redesigned. A vacuum interlock, a translational stage, and an adjustable insertion probe are added to improve the source performance. With these modifications, the source is easier to operate while maximizing sample throughput. In this work, the performance of the newly developed source is examined. The ionization efficiencies are measured with a quadrupole mass spectrometer. The efficiency values obtained with this system are comparable to those obtained from a large scale isotope separator. The relationships among the ionization potential, vapor pressure, and measured ionization efficiency results are discussed. The crucible lifetime has been quantitatively estimated by measuring the crucible sputtering rate. Diagnostic studies of the new source show that the crucible position is a crucial parameter for sensitivity and performance. Stability tests demonstrate that the source can be run several weeks at a fixed emission current without significant degradation.     

Gas‐phase fragmentation of γ‐lactone derivatives by electrospray ionization tandem mass spectrometry

Fragmentation reactions of β‐hydroxymethyl‐, β‐acetoxymethyl‐ and β‐benzyloxymethyl‐butenolides and the corresponding γ‐butyrolactones were investigated by electrospray ionization tandem mass spectrometry (ESI‐MS/MS) using collision‐induced dissociation (CID). This study revealed that loss of H₂O [M + H ?18]⁺ is the main fragmentation process for β‐hydroxymethylbutenolide (1) and β‐hydroxymethyl‐γ‐butyrolactone (2). Loss of ketene ([M + H ?42]⁺) is the major fragmentation process for protonated β‐acetoxymethyl‐γ‐butyrolactone (4), but not for β‐acetoxymethylbutenolide (3). The benzyl cation (m/z 91) is the major ion in the ESI‐MS/MS spectra of β‐benzyloxymethylbutenolide (5) and β‐benzyloxymethyl‐γ‐butyrolactone (6). The different side chain at the β‐position and the double bond presence afforded some product ions that can be important for the structural identification of each compound. The energetic aspects involved in the protonation and gas‐phase fragmentation processes were interpreted on the basis of thermochemical data obtained by computational quantum chemistry. Copyright © 2009 John Wiley & Sons, Ltd.     

Fingerprinting of yogurt products by laser desorption spray post‐ionization mass spectrometry

Yogurt and related products have been directly analyzed using laser desorption spray post‐ionization mass spectrometry (LDSPI‐MS) in positive ion mode. Assignments are made for some of the abundant diagnostic peaks through LDSPI‐MS/MS analysis in comparison with authentic compounds. It is demonstrated that different yogurt products can be reliably differentiated according to their LDSPI‐MS spectra. Principal component analysis (PCA) is further used to clearly show the capability of LDSPI‐MS fingerprinting for rapid sorting of yogurt products. We believe that this sample‐preparation‐free technique can be a very useful product screening tool in the dairy industry because of its simplicity, reliability and high throughput. Copyright © 2010 John Wiley & Sons, Ltd.     

Organization of nucleobase‐functionalized β‐peptides investigated by soft electrospray ionization mass spectrometry

The development and validation of analytical methods is a key to succeed in investigating noncovalent interactions between biomolecules or between small molecules and biomolecules. Electrospray ionization mass spectrometry (ESI‐MS) was applied with a Fourier transform ion cyclotron resonance mass spectrometer (FTICR‐MS) as well as a quadrupole/time‐of‐flight tandem mass spectrometer (QqToF‐MS) for a systematic investigation of noncovalent complexes based on nucleobase pairing in an artificial and noncharged backbone topology. Synthetical β‐peptide helices covalently modified with nucleobases were organized by recognition of a sequence of four nucleobases. Specific duplexes of β‐peptide helices were obtained on the basis of hydrogen bonding base pair complementarity. Oligomer interactions were detected with defined stoichiometry and sensitivity for the respective duplex stability. FTICR‐MS and QqToF‐MS were used equally well to indicate double strand stabilities in agreement with the dissociation data determined by UV spectroscopy. Furthermore, the dissociation energies of gas phase ions of the noncovalent complexes were analyzed with collision induced dissociation (CID)‐MS/MS and infrared multiphoton dissociation (IRMPD)‐MS/MS. The CID conditions turned out to be too harsh for a differentiation of the duplex stabilities, whereas IRMPD might be developed as a technique to detect even small interaction energy differences. Copyright © 2009 John Wiley & Sons, Ltd.     

On‐surface Fenton and Fenton‐like reactions appraised by paper spray ionization mass spectrometry

On‐surface degradation of sildenafil (an adequate substrate as it contains assorted functional groups in its structure) promoted by the Fenton (Fe²⁺/H₂O₂) and Fenton‐like (Mⁿ⁺/H₂O₂; Mⁿ⁺ = Fe³⁺, Co²⁺, Cu²⁺, Mn²⁺) systems was investigated by using paper spray ionization mass spectrometry (PS‐MS). The performance of each system was compared by measuring the ratio between the relative intensities of the ions of m/z 475 (protonated sildenafil) and m/z 235 (protonated lidocaine, used as a convenient internal standard and added to the paper just before the PS‐MS analyzes). The results indicated the following order in the rates of such reactions: Fe²⁺/H₂O₂ ≫ H₂O₂ ≫ Cu²⁺/H₂O₂ > Mⁿ⁺/H₂O₂ (Mⁿ⁺ = Fe³⁺, Co²⁺, Mn²⁺) ~ Mⁿ⁺ (Mⁿ⁺ = Fe²⁺, Fe³⁺, Co²⁺, Cu²⁺, Mn²). The superior capability of Fe²⁺/H₂O₂ in causing the degradation of sildenafil indicates that Fe²⁺ efficiently decomposes H₂O₂ to yield hydroxyl radicals, quite reactive species that cause the substrate oxidation. The results also indicate that H₂O₂ can spontaneously decompose likely to yield hydroxyl radicals, although in a much smaller extension than the Fenton system. This effect, however, is strongly inhibited by the presence of the other cations, ie, Fe³⁺, Co²⁺, Cu²⁺, and Mn²⁺. A unique oxidation by‐product was detected in the reaction between Fe²⁺/H₂O₂ with sildenafil, and a possible structure for it was proposed based on the MS/MS data. The on‐surface reaction of other substrates (trimethoprim and tamoxifen) with the Fenton system was also investigated. In conclusion, PS‐MS shows to be a convenient platform to promptly monitor on‐surface oxidation reactions.     

Stereochemical effects in mass spectrometry. 3—Detection of chirality by chemical ionization mass spectrometry

It was found that the chemical ionization mass spectra of the enantiomers of some α-amino acids and α-hydroxy acids could be definitely distinguished when a chiral compound, l-amyl alcohol, was used as a component of the reagent gases. The relative abundances of some characteristic ions produced through ion-molecule reactions in the gas phase were much higher in the D isomers than in the L isomers. The results were highly reproducible. This approach proved to be a convenient way for the detection of the chirality of these compounds by chemical ionization mass spectrometry.     

Vibrating tip spray ionization mass spectrometry for direct sample analysis

In this work, a vibrating tip spray ionization source was developed for direct mass spectrometric analysis of raw samples under voltage‐free condition. A solid tip was mounted on a vibrator, and the solid tip was placed on the front of MS inlet. Liquid, viscous, and bulk solid samples could be directly loaded on the tip‐end surface, and then a drop of solvent at microliter level was subsequently loaded on the tip for dissolution and extraction of analytes, and a vibrator was then started to atomize and ionize the analytes under ambient condition. We demonstrated vibrating tip spray mass spectrometry in various applications, including food safety, pharmaceutical analysis, and forensic science. Furthermore, in situ analysis of biological tissues and in vivo analysis of living plants were conveniently performed, due to voltage‐free. Different vibration frequencies and solvent compositions were investigated. The analytical performances, including sensitivity, reproducibility, and linear range, were investigated. The ionization process and mechanism were also discussed in this work.     

Real time monitoring of accelerated chemical reactions by ultrasonication‐assisted spray ionization mass spectrometry

Ultrasonication has been used to accelerate chemical reactions. It would be ideal if ultrasonication‐assisted chemical reactions could be monitored by suitable detection tools such as mass spectrometry in real time. It would be helpful to clarify reaction intermediates/products and to have a better understanding of reaction mechanism. In this work, we developed a system for ultrasonication‐assisted spray ionization mass spectrometry (UASI–MS) with an ~1.7 MHz ultrasonic transducer to monitor chemical reactions in real time. We demonstrated that simply depositing a sample solution on the MHz‐based ultrasonic transducer, which was placed in front of the orifice of a mass spectrometer, the analyte signals can be readily detected by the mass spectrometer. Singly and multiply charged ions from small and large molecules, respectively, can be observed in the UASI mass spectra. Furthermore, the ultrasonic transducer used in the UASI setup accelerates the chemical reactions while being monitored via UASI–MS. The feasibility of using this approach for real‐time acceleration/monitoring of chemical reactions was demonstrated. The reactions of Girard T reagent and hydroxylamine with steroids were used as the model reactions. Upon the deposition of reactant solutions on the ultrasonic transducer, the intermediate/product ions are readily generated and instantaneously monitored using MS within 1 s. Additionally, we also showed the possibility of using this reactive UASI–MS approach to assist the confirmation of trace steroids from complex urine samples by monitoring the generation of the product ions. Copyright © 2014 John Wiley & Sons, Ltd.     

Ultrasonication-assisted spray ionization mass spectrometry for on-line monitoring of organic reactions

A straightforward on-line monitoring of organic reactions by ultrasonication-assisted spray ionization mass spectrometry (UASI MS) is demonstrated in this work.     

Ultrasonication-assisted spray ionization mass spectrometry for the analysis of biomolecules in solution

In this paper, we describe a novel technique—ultrasonication-assisted spray ionization (UASI)—for the generation of singly charged and multiply charged gas-phase ions of biomolecules (e.g., amino acids, peptides, and proteins) from solution; this method employs a low-frequency ultrasonicator (ca. 40 kHz) in place of the high electric field required for electrospray ionization. When a capillary inlet is immersed into a sample solution within a vial subjected to ultrasonication, the solution is continually directed to the capillary outlet as a result of ultrasonication-assisted capillary action; an ultrasonic spray of the sample solution is emitted at the outlet of the tapered capillary, leading to the ready generation of gas-phase ions. Using an ion trap mass spectrometer, we found that singly charged amino acid and multiply charged peptides/proteins ions were generated through this single-step operation, which is both straightforward and extremely simple to perform. The setup is uncomplicated: only a low-frequency ultrasonicator and a tapered capillary are required to perform UASI. The mass spectra of the multiply charged peptides and proteins obtained from sample solutions subjected to UASI resemble those observed in ESI mass spectra.     

Laser desorption dual spray post‐ionization mass spectrometry for direct analysis of samples via two informative channels

A laser desorption dual spray post‐ionization mass spectrometry method is described, and its usefulness is demonstrated with the examples of selective detection of food components, manipulation of protein charge state distribution and investigation on the formation of magic number clusters. The method is carried out by adopting two spray emitters for post‐ionization of analytes desorbed by a pulsed infrared laser. Various components in a complex sample or distinct behavior of an analyte in two different spray reagents can be rapidly probed by the method quasi‐simultaneously, highlighting the potential applications of this method for protein characterization, reaction study and food analysis. Copyright © 2013 John Wiley & Sons, Ltd.     

Desorption electrospray ionization ‐ orbitrap mass spectrometry of synthetic polymers and copolymers

Desorption ElectroSpray Ionization (DESI) ‐ Orbitrap Mass Spectrometry (MS) was evaluated as a new tool for the characterization of various industrial synthetic polymers (poly(ethylene glycol), poly(propylene glycol), poly(methylmethacrylate), poly(dimethylsiloxane)) and copolymers, with masses ranging from 500 g.mol⁻¹ up to more than 20 000 g.mol⁻¹. Satisfying results in terms of signal stability and sensitivity were obtained from hydrophobic surfaces (HTC Prosolia) with a mixture water/methanol (10/90) as spray solvent in the presence of sodium salt. Taking into account the formation of multiplied charged species by DESI‐MS, a strategy based on the use of a deconvolution software followed by the automatic assignment of the ions was described allowing the rapid determination of M_n, M_w and PDI values. DESI‐Orbitrap MS results were compared to those obtained from matrix‐assisted laser desorption/ionization‐ time‐of‐flight MS and gel permeation chromatography. An application of DESI‐Orbitrap MS for the detection and identification of polymers directly from cosmetics was described. Copyright © 2012 John Wiley & Sons, Ltd.