Time Of Flight Mass Analyzer Research Articles

Development of High-Resolution Photoelectron Imaging with Dual-Reflection Time of Flight Mass Analyzer

Development of High-Resolution Photoelectron Imaging with Dual-Reflection Time of Flight Mass Analyzer

Parallel Operation of Electron Ionization and Chemical Ionization for GC-MS Using a Single TOF Mass Analyzer.

This work describes a novel mass spectrometer coupled to gas chromatography (GC-MS) that simultaneously displays the mass spectral information of electron (EI)- and chemical ionization (CI)-generated ion populations for a single chromatographic peak. After GC separation, the eluent is equally split and supplied in parallel to an EI and a novel CI source, both operating continuously. Precise switching of the ion optics provides the exact timing to consecutively extract the respective ion population from both sources and transfer them into a time-of-flight (TOF) mass analyzer. This technique enables the acquisition of complementary information from both ion populations (EI and CI) within a single chromatographic run and with sufficient data points to retain the chromatographic fidelity. The carefully designed GC transfer setup, fast ion optical switching, and synchronized TOF data acquisition system provide an automatic and straightforward spectral alignment of two ion populations. With an eluent split ratio of about 50% between the two ion sources, instrument detection limits of <40 fg on the column (octafluoronaphthalene) for the EI and <2 pg (benzophenone) for the CI source were obtained. The system performance and the additional analytical value for compound identification are demonstrated by means of different common GC standard mixtures and a commercial perfume sample of unknown composition.

Online analysis of chemical composition and size distribution of fresh cigarette smoke emitted from a heated tobacco product

Online analysis of chemical composition of cigarette smoke of a heated tobacco product (HTP) was performed by using a home-made vacuum ultraviolet (VUV) lamp-based photoionization time-of-flight (TOF) mass spectrometer. A capillary inlet and an aerodynamic lens were utilized to sample the gas- and particulate-phase of the HTP smoke, without dilution and pretreatment, which can be switched from each other within minutes. A thermal desorption unit was installed to vaporize the particulate-phase into gas and its vaporization temperature was determined, based on an equilibrium between the evaporation efficiency and the thermal decomposition of organic compounds. Then these species were softly ionized by VUV photons and their ions were measured by a reflectron TOF mass analyzer. Meanwhile, the puff-by-puff resolved size distributions of the HTP smoke were probed with a commercial scanning mobility particle sizers (SMPS). The mean diameters of particles firstly increase with the puff number, mainly located in the range of 200 – 300 nm, and then approached a steady state. This method was validated to measure the physical-chemical characteristics of the HTP cigarette smoke.•A capillary inlet and an aerodynamic lens were utilized to sample the gas- and particulate-phase of the HTP smoke.•Chemical composition of the HTP smoke was measured by using a compact VUV photoionization mass spectrometer.•The particle size distribution of the HTP smoke without dilution was measured online.

Identification and structural characterization of potential degraded impurities of ribociclib by time of flight -tandem mass spectrometry, and their toxicity prediction

The US FDA and EMA approved Ribociclib (RIBO) to treat metastatic breast cancers in 2017. Formation of impurities during storage of any drug can significantly contribute to its overall toxicity and therapeutic efficacy, which ultimately leads to a safety concern. Over the period, it has been observed that impurities sometimes cause serious unwanted toxicity, which can even lead to withdrawal of a drug from market. Therefore, complete characterization of potential impurities is extremely important to identify molecular hot spots regarding structural changes. To the best of our knowledge, till date, the potential degraded impurities of RIBO are unknown. No study reported in literature on the structural characterization of the degradation impurities of RIBO. In this study, an ICH recommended comprehensive stress study under hydrolytic, oxidative, photolytic and thermolytic conditions was performed on RIBO. The degradation products were characterized by tandem mass spectrometry utilising time of flight mass analyzer majorly after electrospray ionisation. The atmospheric pressure chemical ionisation mode was employed in characterization of the N-oxide degradation products where Meisenheimer rearrangement occurred. A degradation product was synthesized in house and fully characterized with the help of NMR (1H NMR, 13C NMR, DEPT, 2D NMR and D2O exchange experiments). The source of formylation for the generation of degradation products was investigated employing different solvent systems. The degradation pathways were delineated by explaining the putative mechanism of degradation in various conditions. The in silico toxicity of the degradation impurities was evaluated with the help of ProTox-II toxicity prediction platform.

Unveiling the Molecular Basis of Mascarpone Cheese Aroma: VOCs analysis by SPME-GC/MS and PTR-ToF-MS.

Mascarpone, a soft-spread cheese, is an unripened dairy product manufactured by the thermal-acidic coagulation of milk cream. Due to the mild flavor and creamy consistency, it is a base ingredient in industrial, culinary, and homemade preparations (e.g., it is a key constituent of a widely appreciated Italian dessert ‘Tiramisù’). Probably due to this relevance as an ingredient rather than as directly consumed foodstuff, mascarpone has not been often the subject of detailed studies. To the best of our knowledge, no investigation has been carried out on the volatile compounds contributing to the mascarpone cheese aroma profile. In this study, we analyzed the Volatile Organic Compounds (VOCs) in the headspace of different commercial mascarpone cheeses by two different techniques: Headspace-Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry (HS-SPME GC-MS) and Proton-Transfer Reaction-Mass Spectrometry coupled to a Time of Flight mass analyzer (PTR-ToF-MS). We coupled these two approaches due to the complementarity of the analytical potential—efficient separation and identification of the analytes on the one side (HS-SPME GC-MS), and effective, fast quantitative analysis without any sample preparation on the other (PTR-ToF-MS). A total of 27 VOCs belonging to different chemical classes (9 ketones, 5 alcohols, 4 organic acids, 3 hydrocarbons, 2 furans, 1 ester, 1 lactone, 1 aldehyde, and 1 oxime) have been identified by HS-SPME GC-MS, while PTR-ToF-MS allowed a rapid snapshot of volatile diversity confirming the aptitude to rapid noninvasive quality control and the potential in commercial sample differentiation. Ketones (2-heptanone and 2-pentanone, in particular) are the most abundant compounds in mascarpone headspace, followed by 2-propanone, 2-nonanone, 2-butanone, 1-pentanol, 2-ethyl-1-hexanol, furfural and 2-furanmethanol. The study also provides preliminary information on the differentiation of the aroma of different brands and product types.

Top-down protein identification using a time-of-flight mass spectrometer and data independent acquisition

Top-down mass spectrometry and direct dissociation of gas phase intact proteins have been demonstrated to be a powerful platform for identifying proteins from complex mixtures and for elucidating post-translational modifications (PTMs). Fragmentation of proteins in the atmospheric pressure/vacuum interface of the electrospray ionization mass spectrometer is an effective dissociation technique that can be utilized for on-line HPLC top-down analysis. We demonstrate the capability to perform intact protein identifications in a single-stage time-of-flight (TOF) mass spectrometer in a data independent (DIA) acquisition fashion by rapidly switching the in-source dissociation (ISD) energy during protein elution from a liquid chromatography (LC) column. The intact protein and product ion masses obtained at low and high ISD energies, respectively, were measured using a TOF mass analyzer. By coupling on-line protein separations to dissociation in the atmospheric pressure/vacuum interface region of the mass spectrometer, we identified proteins in simple complexity mixtures, including subunits from the human 20S proteasome complex, and PTMs such as phosphorylation and N-terminal acetylation events. This proof-of-principle study demonstrates that a data-independent pseudo-MS/MS method could be a relatively inexpensive platform for top-down MS.

Suspect Screening Using LC-QqTOF Is a Useful Tool for Detecting Drugs in Biological Samples.

High-resolution mass spectrometers (HRMS), including quadrupole time of flight mass analyzers (QqTOF), are becoming more prevalent as screening tools in clinical and forensic toxicology laboratories. Among other advantages, HRMS instruments can collect untargeted, full-scan mass spectra. These datasets can be analyzed retrospectively using a combination of techniques, which can extend the drug detection capabilities. Most laboratories using HRMS in production settings perform untargeted data collection, but analyze data in a targeted manner. To perform targeted analysis, a laboratory must first analyze a reference standard to determine the expected characteristics of a given compound. In an alternate technique known as suspect screening, compounds can be tentatively identified without the use of reference standards. Instead, predicted and/or intrinsic characteristics of a compound, such as the accurate mass, isotope pattern, and product ion spectrum are used to determine its presence in a sample. The fact that reference standards are not required a priori makes this data analysis approach very attractive, especially for the ever-changing landscape of novel psychoactive substances. In this work, we compared the performance of four data analysis workflows (targeted and three suspect screens) for a panel of 170 drugs and metabolites, detected by LC-QqTOF. We found that retention time was not required for drug identification; the suspect screen using accurate mass, isotope pattern, and product ion library matching was able to identify more than 80% of the drugs that were present in human urine samples. We showed that the inclusion of product ion spectral matching produced the largest decrease in false discovery and false negative rates, as compared to suspect screening using mass alone or using just mass and isotope pattern. Our results demonstrate the promise that suspect screening holds for building large, economical drug screens, which may be a key tool to monitor the use of emerging drugs of abuse, including novel psychoactive substances.

Letter: A method for the chromatic aberration correction of a laser time of-flight mass analyzer.

The new ion-optical system of the laser time-of-flight (TOF) mass spectrometer on the basis of two tandem wedge-shape reflectors has been offered and implemented. A new method of correcting chromatic aberration by the ion energy was proposed that used a wire electrode unit with adjustable potentials. This unit allows one to adjust the local TOF of the ions in a narrow energy range ± (1-2)% within the total ion packet with an energy spread of ± 20%. The method reduces the duration of the ion packets by up to 1.5ns, which enables us to obtain the restriction of resolution at a level not worse than R ~ 10500 for a TOF ~35 µs. The aim of the project is to increase the separation of isobaric ions to improve the limit of detection of the laser TOF-MS for the analysis of high-purity samples.

Biomarkers discovery by peptide and protein profiling in biological fluids based on functionalized magnetic beads purification and mass spectrometry.

Biomarkers discovery by peptide and protein profiling in biological fluids based on functionalized magnetic beads purification and mass spectrometry.

A novel two-laser interface for coupling capillary electrochromatography with ion-trap time-of-flight mass spectrometry

An interface has been developed for the hyphenation of capillary electrochromatography (CEC) with mass spectrometry (MS). Chromatographic eluate vaporization and selective analyte ionization occur within a quadrupole ion-trap, which permits significant instrument simplification when compared with the atmospheric pressure interfaces typically used for CEC–MS. Vaporization is achieved using laser desorption at 1064nm while ionization is accomplished through UV photoionization. This two-step approach, through ionization laser wavelength selection, can provide ultratrace analysis with high selectivity. The mass spectrometer is a hybrid ion-trap time-of-flight (TOF) instrument in which the ion-trap is used in radio frequency-only mode, with DC-pulse ejection, to provide decoupling of the different timescales required for CEC separation and TOF mass analysis. The ion-trap is capable of accumulating ions over multiple laser shots. The mass resolution of the demonstration instrument was circa 1500. Preliminary CEC–MS runs have been recorded for mixtures containing polycyclic aromatic hydrocarbons. A concentration detection limit of 500nM, for naphthalene in acetonitrile, has been determined for the interface.

Study of organic contamination induced by outgassing materials. Application to the Laser MégaJoule optics

Organic contamination may decrease the targeted performances of coated surfaces. To study the contamination induced by surrounding materials, a method using a thermal extractor is presented in the first part of this work. Besides its normal operation (analyses of outgassing compounds from a material), this device is used in an original way to contaminate and decontaminate samples. Efficiency of contamination and decontamination protocols are assessed by automated thermal desorption and gas chromatography coupled with mass spectrometry and by secondary ion mass spectrometry coupled with a time of flight mass analyzer. This enables to study the contamination induced by a bulk material outgassing and to take in consideration the possible competition between outgassed species. This method is then applied to investigate contamination of Laser MégaJoule sol–gel coated optics by a retractable sheath. The impact of the temperature on the outgassing of the sheath has been highlighted. Increasing temperature from 30 to 50°C enables the outgassing of organophosphorous compounds and increases the outgassing of oxygenated compounds and phthalates. Chemical analyses of contaminated optics have highlighted affinities between the sol–gel coating and phthalates and organophosphorous, and low affinities with aromatics and terpens. Finally, samples with increasing levels of contamination have been realized. However a saturation phenomenon is observed at 90ngcm–2.

Mass Spectrometry in Russia

The present review covers the main research in the area of mass spectrometry from the 1990s which was about the same time as the Russian Federation emerged from the collapse of the Soviet Union (USSR). It consists of two main parts-application of mass spectrometry to chemistry and related fields and creation and development of mass spectrometric technique. Both traditional and comparatively new mass spectrometric methods were used to solve various problems in organic chemistry (reactivity of gas-phase ions, structure elucidation and problems of identification, quantitative and trace analysis, differentiation of stereoisomers, derivatization approaches etc.), biochemistry (proteomics and peptidomics, lipidomics), medical chemistry (mainly the search of biomarkers, pharmacology, doping control), environmental, petrochemistry, polymer chemistry, inorganic and physical chemistry, determination of natural isotope ratio etc. Although a lot of talented mass spectrometrists left Russia and moved abroad after the collapse of the Soviet Union, the vitality of the mass spectral community proved to be rather high, which allowed the continuation of new developments in the field of mass spectrometric instrumentation. They are devoted to improvements in traditional magnetic sector mass spectrometers and the development of new ion source types, to analysis and modification of quadrupole, time-of-flight (ToF) and ion cyclotron resonance (ICR) analyzers. The most important achievements are due to the creation of multi-reflecting ToF mass analyzers. Special attention was paid to the construction of compact mass spectrometers, particularly for space exploration, of combined instruments, such as ion mobility spectrometer/mass spectrometer and accelerating mass spectrometers. The comparatively young Russian Mass Spectrometry Society is working hard to consolidate the mass spectrometrists from Russia and foreign countries, to train young professionals on new appliances and regularly holds conferences on mass spectrometry. For ten years, a special journal Mass-spektrometria has published papers on all disciplines of mass spectrometry.

Matrix Assisted Ionization Vacuum (MAIV), a New Ionization Method for Biological Materials Analysis Using Mass Spectrometry

The introduction of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) for the mass spectrometric analysis of peptides and proteins had a dramatic impact on biological science. We now report that a wide variety of compounds, including peptides, proteins, and protein complexes, are transported directly from a solid-state small molecule matrix to gas-phase ions when placed into the vacuum of a mass spectrometer without the use of high voltage, a laser, or added heat. This ionization process produces ions having charge states similar to ESI, making the method applicable for high performance mass spectrometers designed for atmospheric pressure ionization. We demonstrate highly sensitive ionization using intermediate pressure MALDI and modified ESI sources. This matrix and vacuum assisted soft ionization method is suitable for the direct surface analysis of biological materials, including tissue, via mass spectrometry.

Effects of retinoic acid isomers on proteomic pattern in human breast cancer MCF-7 cell line

Retinoids, acting through their cognate nuclear receptors, are crucial transcriptional regulators of many cellular processes such as differentiation, development, apoptosis, carbohydrate and lipid metabolism, homeostasis, etc. The aim of this study was the exploration of molecular mechanisms in relation to therapy of human breast cancer. One of the efficient strategies is identification of biomarkers as important tools in early cancer diagnosis and advisable treatment. Retinoids have been regarded as important therapeutic agents for many types of cancers, including human breast cancer. The effects of all-trans retinoic acid and 9-cis retinoic acid or their combination on proteomic pattern in human MCF-7 breast cancer line were investigated. The total cell proteins were extracted utilizing a commercially Radio-Immunoprecipitation Assay (RIPA) buffer and separated on 1D sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D SDS-PAGE). The proteins were subsequently digested in-gel by trypsin and identified by matrix assisted laser desorption ionization technique with time of flight mass analyzer (MALDI-TOF/TOF). Our data offer novel information on the proteomic pattern of proteins evaluated after treatment of MCF-7 cells with retinoic acid isomers.

Development of Orthogonal Acceleration Time-of-Flight Mass Spectrometer for Detection of Ions with Wide Energies Distribution

A wide detection range of ion energy time-of-flight(TOF) mass spectrometer was developed successfully.The instrument coupled associated with electron impact source,ions flow was modulated effectively by a lens system,and then introduced into time-of-flight mass analyzer,which had dual field of acceleration region and reflection region,and a large-size microchannel plate(MCP) detection device.Half-peak width of single ion signal is about 2 ns,resolution of the instrument is better than 1600 FWHM,mass range of actual samples is 1-127amu(theoretical mass detection limit could be higher than 800 amu),ion energy detection range is better than two orders of magnitude(3-140 eV).If couple associated with short-instantaneous pulse discharge ion source,the TOF mass analyzer could be used in the field of rapid detection of high-energy ion beam,such as vacuum cathode discharge preparation of thin films,ion injection material characterization,the ion charge state distribution of conductive material and determination of ion diffusion speed.

Linking GC-MS and PTR-TOF-MS fingerprints of food samples

Recently the first applications in food science and technology of the newly available volatile organic compound (VOC) detection technique proton transfer reaction‐mass spectrometry, coupled with a time of flight mass analyzer (PTR-TOF-MS), have been published. In comparison with standard techniques such as GC-MS, PTR-TOF-MS has the remarkable advantage of being extremely fast but has the drawback that compound identification is more challenging and often not possible without further information. In order to better exploit and understand the analytical information entangled in the PTR-TOF-MS fingerprint and to link it with SPME/GC-MS analyses we employed two multivariate calibration methods, PLS and the more recent LASSO. We show that, while in some cases it is sufficient to consider a single PTR-TOF-MS peak in order to predict the intensity of a SPME/GC-MS peak, in general a multivariate approach is needed. We compare the performances of PLS and LASSO in terms of prediction capabilities and interpretability of the model coefficients and conclude that LASSO is more suitable for this problem. As case study, we compared GC and PTR-MS data for different matrices, namely olive oil and grana cheese.

Using 2-D electrophoresis followed by nano HPLC in nuclear protein analysis of MCF-7 breast cancer cell line by MALDI-TOF/TOF

Abstract The biomarker identification is an important tool in early cancer detection. The MCF-7 breast cancer cell line was chosen as a model system. The nuclear proteins were extracted utilizing a commercially manufactured kit and separated on two dimensional (2-D) sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). The first dimension was performed on isoelectric focusing strips with pH range 4–7. Afterwards the proteins were tryptic digested and identification was performed by matrix assisted laser desorption technique with time of flight mass analyzer (MALDI-TOF/TOF). For unambiguous identification proteins with too low concentration or spots contains protein mixture the nano high performance liquid chromatography (HPLC) was used. The 2-D gel electrophoresis (2-DGE) seems to be a good tool to separate large amount of proteins using relatively simple procedure and its hyphenation with HPLC can create the perfect analytical solution for proteome identification. About 150 nuclei protein spots were visualized and the most abundant of them were identified.

Optimization of a quadrupole ion storage trap as a source for time‐of‐flight mass spectrometry

Designs of a quadrupole ion trap (QIT) as a source for time-of-flight (TOF) mass spectrometry are evaluated for mass resolution, ion trapping, and laser activation of trapped ions. Comparisons are made with the standard hyperbolic electrode ion trap geometry for TOF mass analysis in both linear and reflectron modes. A parallel-plate design for the QIT is found to give significantly improved TOF mass spectrometer performance. Effects of ion temperature, trapped ion cloud size, mass, and extraction field on mass resolution are investigated in detail by simulation of the TOF peak profiles. Mass resolution (m/Δm) values of several thousand are predicted even at room temperature with moderate extraction fields for the optimized design. The optimized design also allows larger radial ion collection size compared with the hyperbolic ion trap, without compromising the mass resolution. The proposed design of the QIT also improves the ion-laser interaction volume and photon collection efficiency for fluorescence measurements on trapped ions.

Inhibition of pyrene biotransformation by piperonyl butoxide and identification of two pyrene derivatives in Lumbriculus variegatus (Oligochaeta)

Using the freshwater annelid Lumbriculus variegatus (Oligochaeta), the presence of cytochrome P450 (CYP) isozymes was investigated by analyzing metabolites of the polycyclic aromatic hydrocarbon (PAH) pyrene in treatments with and without the CYP inhibitor piperonyl butoxide (PBO). The results show a low biotransformation capability of L. variegatus (7% of total pyrene body burden as metabolites at 168 h). Addition of PBO resulted in a significant reduction of metabolites, suggesting the presence of a CYP in L. variegatus. Besides 1-hydroxypyrene, three peaks representing unknown metabolites were detected in LC-FLD (liquid chromatography with fluorescence detection) chromatograms of L. variegatus. Deconjugations showed that sulfonation and glucosidation are involved in the formation of these unknowns. Further studies with the time of flight mass analyzer provided the identification of the glucose-sulfate conjugate of 1-hydroxypyrene. The same metabolites were detected in the solvent-nonextractable fraction by incubation of the tissue residues with proteinase K, suggesting that part of these metabolites are bound to proteins. Overall, the slow biotransformation of pyrene by L. variegatus (involving CYP) supports the use of this species in standard bioaccumulation tests; however, the tissue-bound metabolite fraction described in the current study deserves further investigation for its toxicity and availability to upper trophic levels through diet.

Novel approaches in analysis of Fusarium mycotoxins in cereals employing ultra performance liquid chromatography coupled with high resolution mass spectrometry

Rapid, simple and cost-effective analytical methods with performance characteristics matching regulatory requirements are needed for effective control of occurrence of Fusarium toxins in cereals and cereal-based products to which they might be transferred during processing. Within this study, two alternative approaches enabling retrospective data analysis and identification of unknown signals in sample extracts have been implemented and validated for determination of 11 major Fusarium toxins. In both cases, ultra-high performance liquid chromatography (U-HPLC) coupled with high resolution mass spectrometry (HR MS) was employed. 13C isotopically labeled surrogates as well as matrix-matched standards were employed for quantification. As far as time of flight mass analyzer (TOF-MS) was a detection tool, the use of modified QuEChERS (quick easy cheap effective rugged and safe) sample preparation procedure, widely employed in multi-pesticides residue analysis, was shown as an optimal approach to obtain low detection limits. The second challenging alternative, enabling direct analysis of crude extract, was the use of mass analyzer based on Orbitrap technology. In addition to demonstration of full compliance of the new methods with Commission Regulation (EC) No. 401/2006, also their potential to be used for confirmatory purposes according to Commission Decision 2002/657/EC has been critically assessed.