Phthalate esters, frequently used as plasticizers in consumer products, raise concerns because of potential health effects. Using density functional theory (DFT) with BLYP and 6-311++G(d, p) basis sets, their properties, such as dipole moment, polarizability, proton affinity and ionization energy of phthalate esters are obtained. Reaction kinetics and thermodynamics of popular reagent ions like HO, NH, NO and O are computed to know the feasibility of the reactions with such ions. Proton affinity and ionization energy indicate high susceptibility to proton and charge transfer reactions. High dipole moments contribute to elevated rate coefficients in proton transfer reaction mass spectrometry (PTR-MS) and selected ion flow tube mass spectrometry (SIFT-MS). PTR-MS rates are influenced by drift tube conditions, supported by high center-of-mass collisional energy of E = 0.28 eV. SIFT-MS rates diminish with rising temperature. The high kinetic energy data of HO, NO and O suggests that simple proton transfer and charge transfer reactions are overruled due to very high internal energy which could lead to extensive fragmentation of phthalate esters. The energetic profile of NH ions indicates their suitability for quantifying phthalate esters using NH-CI-MS techniques.

This article presents a relationship between the size of an ion crystal in a Paul trap and the radio frequency potential applied on the central ring electrode. Using a simple and elegant derivation it has been shown that the distance of an ion in the crystal from the trap center is proportional to power of the applied radio frequency voltage. The validity of this power law has been demonstrated on ion crystals having up to 13 ions. A spring-mass model has been presented to predict structure of ion crystals in Paul traps operating in the Dehmelt regime. Structures are obtained by minimizing the total potential energy stored in an ion ensemble. The total potential energy is taken to be the sum of the electrostatic potential due to ion-ion interaction and the potential energy stored in the springs. Structures of crystals having up to 13 ions predicted by our model have been verified by comparing them with results obtained by direct numerical simulations.

Gels created by self-assembly of small organic molecules are dynamic soft materials that have unique properties and demanding characterization. Four chiral gelators, with two valinol- or leucinoloxamido arms attached to the 2,2'-positions of the proatropisomeric biphenyl group were chosen to show that the electrospray ionization mass spectrometry (ESI-MS) could be used to differentiate the gelation feature of the chiral compounds and also to shed light on the gelation processes. By inspecting the gelation of several solvents, we showed that () proved to be the most efficient gelator, forming the largest observable assemblies in the gas phase. The strong intermolecular H-bonds hold single-charged assemblies consisting of up to five monomer units detectable by ESI MS. Enantiomer () is a good gelator due to favorable intramolecular interactions that remain preserved in the gas phase. ompound () does not have gelator properties and detected signals of larger assemblies in the gas phase. So, the detected signals correlate with the conformations of the studied compounds. MS could be used to elucidate the preferential type of noncovalent interaction due to the chiral recognition. The study paves a novel way to investigate the influence of chirality on the molecular assembly and consequently macroscopic properties and functions of materials.

The dimer and trimer structures of the non-amyloidogenic rat islet amyloid polypeptide 21-37 peptide, formed in an HO/CHOH (1% CHCOOH) solution were investigated using electrospray ionization-tandem mass spectrometry (ESI-MS/MS). The dissociation of monomers, dimers, and trimers was investigated by MS/MS using collision-induced dissociation. The peptide bond dissociation between L and P was mainly observed in the tandem mass spectra of the monomers and oligomers, regardless of the parent ion charge state. The fragment ions were observed as a series of b (u = 3-4, 6-7, 12) or y (n = 10-11, 13-14) in the [Mono + 2H] (=[monomer + 2H]) tandem mass spectrum. MS/MS analysis of the [Di + 3H] (=[dimer + 3H]) complex indicated that [Di + 3H] comprised [Mono + H] and [Mono + 2H] subunits. During covalent bond dissociation of the [Di + 3H] complex, a fragmentation pattern was observed in the form of {mono + (fragment ion of [Mono + 2H])}, resulting from the collision energy dissociation of the [Mono + 2H] peptide. The [(C-terminal)-(C-terminal)] interaction geometry was proposed for the [Di + 3H] complex based on the observation of [y+ y] (n = 10-11, 13-16) fragment ions in the [Di + 3H] tandem mass spectrum. MS/MS analysis of the [Tri + 4H] (=[trimer + 4H]) complex indicated that [Tri + 4H] comprised [Mono + H] and [Di + 3H] subunits. The (monomer-[Di + 3H]) complex geometry was assumed to be stable based on the presence of {mono + (fragment ion of [Di + 3H])} ions in the tandem mass spectrum of the [Tri + 4H] complex. The two [Mono + (y+ y)] and [Mono + (Mono + y)] fragment ions also supported the (monomer-[Di + 3H]) complex geometries of the [Tri + 4H] complex. The [(C-terminal)-(C-terminal)] interaction geometry of the [Di + 3H] subunit is thought to be conserved in the [Tri + 4H] complex geometries.

Mass spectrometry (MS) has become a pivotal analytical tool across various scientific disciplines due to its ability to provide detailed molecular information with high sensitivity and specificity. MS plays a crucial role in various fields, including drug discovery and development, proteomics, metabolomics, environmental analysis, and clinical diagnostics and Forensic science. In this article we are discussing the application of MS across the diverse scientific disciplines by focusing on some classical examples from each field of application. As the technology continues to evolve, it promises to unlock new possibilities in scientific research and practical applications, cementing its position as an essential tool in modern analytical science.

Present work describes the development of a liquid chromatography tandem mass spectrometry-based bioanalytical method for the reliable simultaneous quantification of docetaxel (DXL) and carvacrol (CVL) in the mice plasma. A rapid and sensitive bioanalytical method was developed and optimized in mice plasma using Paclitaxel as an internal standard. Validation of the bioanalytical method was performed according to the ICH M10 guideline covering the range of 9.62-1923.08 ng/mL in the mice plasma milleu at the low, mid, and high-quality control concentrations of 28.86 ng/mL, 961.54 ng/mL, and 1346.15 ng/mL, respectively for both the analytes. Validation parameters such as accuracy, precision, carryover-test, matrix effect, and reinjection reproducibility were carried out and were found in limits. Stability studies (Benchtop, autosampler, freeze-thaw, and long-term) were performed and found to be within limits. The developed bioanalytical method was found to be suitable for the simultaneous quantification of DXL and CVL in the mice plasma.

This paper proposed a dual-layer linear ion trap mass analyzer (dLIT) based on micro-electromechanical systems (MEMS) technology and stacked-layer structure for the development of MEMS mass spectrometry. Its basic performance and potential capabilities were explored by ion trajectory simulations. The theoretical formulas were modified by implementing multipole expansion. The simulation results were confirmed to be highly consistent with theoretical calculations in multiple aspects, including stability diagram, secular frequencies, and mass linearity, with only a deviation of 1-2%. In the boundary ejection mode, close to 100% ejection was achieved in a single dimension by applying extra quadrupole DC voltage. Preliminary simulation results showed that dLIT can achieve a peak width of ∼2 mass units (full width at half maximum, FWHM) for m/z 60 ions even at pressures as high as 50 Pa. Furthermore, the application of AC frequency scanning mode in dLIT was also evaluated, and preliminary simulation results yield a peak width of 0.3-0.4 mass units (FWHM). The dLIT offered several advantages, including high-precision fabrication at the sub-millimeter scale, excellent high-pressure performance, and a clear physical model. It preliminarily proved to be an ideal mass analyzer for MEMS mass spectrometry.

Thermal decomposition and isomerization of 1-butyl and 1-pentyl radical were studied in the temperature range of 500-1480 K on a short time scale of 20-100 µs using flash pyrolysis vacuum ultraviolet single-photon ionization time-of-flight mass spectrometry. 1-Bromobutane and 1-bromopentane were used as precursors for the 1-butyl and 1-pentyl radical, respectively. The reactive intermediates in the thermal dissociation reactions were directly observed. The 1-butyl radical decomposed to ethene and ethyl radical with ethyl radical rapidly losing an H atom to form a second ethene molecule. Loss of H atom from butyl radical was also a significant decomposition channel. Isomerization of 1-butyl via 1,3-H migration was observed as a minor channel at 1380 K and above with a branching ratio of less than 3% at 1430 K. The 1-pentyl radical was observed to decompose mainly by isomerization to 2-pentyl radical followed by β-scission to produce propene and ethyl radicals at temperatures approximately 900 K and below. Above 900 K, β-scission of 1-pentyl to produce ethene and 1-propyl radical became increasingly important. Isomerization to 3-pentyl was verified to be a minor channel.

Exenatide is a synthetic glucagon-like peptide 1 analog, widely used in the management of type 2 diabetes mellitus. The stability of pharmaceutical products is significantly impacted by various environmental stress conditions. The present study reports the development of a validated reverse-phase high-performance liquid chromatography (RP-HPLC) stability-indicating method for the identification of force degradation products (DPs) of synthetic glucagon-like peptide-1 analog Exenatide using UHPLC-Orbitrap fusion mass spectrometer. Force degradation studies were performed by subjecting Exenatide to various stress conditions, such as hydrolytic, oxidative, photolytic and thermal to investigate the stability indicating ability of the method. Significant degradation was observed during acidic, oxidative, photolytic and thermal stress conditions. Exenatide and its major DPs identification and characterization were demonstrated by employing LC-HRMS and MS/MS method. In total, five major stress DPs were characterized, and their fragmentation pathway was proposed using MS/MS studies. Finally, the proposed RP-HPLC method was validated as per ICH guidance.

We consider the operation of a digital linear ion trap with resonance radial ejection and mass selective instability modes. Periodic wave shape has a positive part with amplitude and duration and negative part with amplitude and duration , where is the period. The mapping of the stability diagram, calculations of the well's depth and ion oscillations spectra are presented. The process of resonant excitation of ion oscillations by a dipole sinusoidal signal is studied, as well as ion ejection at the stability boundary. The trajectory method is used for this purpose. It is shown that the mass selectivity of dipole excitation is twice as large for rectangular wave shape compared to sinusoidal wave shape. Increasing the diameter of the round rods of the linear trap gives an increase in the resolving power. The possibility of DIT operation in mass-selective instability mode at the boundary point is discussed.

Gastric cancer (GC) is one of the most malignant tumors with high morbidity and mortality in the world. Compound , a Jiyuan oridonin derivative, exhibited excellent anti-proliferative activity against GC cells. To investigate the gastric cellular response to therapy as a novel drug candidate, we adopted a pseudotargeted metabolomics method to explore metabolic variation in -induced MGC-803 gastric cells using liquid chromatography tandem mass spectrometry combined with multivariate statistical analysis. The results showed that treatment induced significant metabolic changes in the levels of aminoacyl-tRNA biosynthesis, alanine, aspartate and glutamate metabolism, pyrimidine metabolism, and tricarboxylic acid cycle, approximately 80% of the metabolites were down-regulated in the low-dose and high-dose groups including aspartate, tryptophan, sedoheptulose 7-phosphate, succinate, 2'-deoxyadenosine, uridine, cytidine, etc. which can provide evidence for a new therapy of GC.

This paper presents a newly developed high-performance mobile single-photon ionization time-of-flight mass spectrometry (M-SPI-TOFMS) system for on-line analysis and stereoscopic monitoring of complex gas mixtures. The system is designed for stereoscopic imaging to map the distribution of volatile organic compounds (VOCs) and trace their emission sources in urban areas and industrial parks. It mainly consists of a SPI-TOFMS instrument, a customized commercial vehicle, a meteorological five-parameter monitor with GPS, a high-power generator, and an uninterruptible power supply. The SPI technique, using a 118 nm VUV lamp, can ionize compounds with an ionization potential below 10.78 eV. Mass spectra obtained using this technique show the profiles of various VOCs and some inorganic compounds. The VOCs composition information and mobile location data are simultaneously sent to the GIS software. In GIS software, this data is used for real-time stereoscopic imaging of VOC distribution and precise tracking of VOC movement. The system can achieve a spatial data resolution of 0.69 mm at 25 km/h due to the microsecond detection speed of the M-SPI-TOFMS instrument. The laboratory test provides a rapid overview characterization of benzene, toluene, and xylene. The M-SPI-TOFMS has limits of detection and mass resolution of 33.7 pptv and 1060, respectively. Several field applications were carried out using M-SPI-TOFMS at various locations to identify VOC sources near different factories. The M-SPI-TOFMS system has a navigation monitoring speed of 25 km/h with a time resolution of 1 s. The widespread use of this system will provide accurate data to support environmental management departments in formulating VOCs pollution control policies and improving control efficiency.

(SW) Nyl is a lichenized fungi in the family Cladoniaceae producing characteristic secondary metabolites of interest. There are only limited chemical studies relating to the genus A chemical study of the lichen was conducted and their chemical constituents were elucidated by ultra-performance liquid chromatography-electrospray ionization/triple-quadrupole tandem-mass spectrometry analysis. It is the first time report of structure analysis of its metabolite by liquid chromatography-mass spectrometry/mass spectrometry. The molecular masses for 20 compounds were detected from different fractions. Seven compounds were elucidated with mass spectrometry/mass spectrometry fragmentation pattern analysis. Barbatic acid () was identified as the major compound being common to all fractions. The identified compounds belong to depsides (, , and ), dibenzofurans (, ) and sugar derivatives () which are usually distributed in lichens.

Phenylketonuria (PKU) is an autosomal genetic disorder caused by a deficiency of the phenylalanine hydroxylase (PAH) enzyme. The lack of PAH results in the inability of phenylalanine (PHE) to transform into tyrosine (TYR). Consequently, this leads to the accumulation of PHE in the blood samples of newborns causing metabolic diseases such as irreversible neurological problems. An analysis was required for determining the values of PHE and TYR in blood samples from newborn babies. In this study, therefore, we developed a derivatized method to monitor PHE and TYR in plasma samples using liquid phase chromatography linked with quadrupole mass spectrometry. Accessible formaldehyde isotopes and cyanoborohydride were used to react with PHE and TYR amino groups to generate -formaldehyde-modified PHE and TYR (as standards) and -formaldehyde-modified PHE and TYR (as internal standards). We used tandem mass spectrometry for multiple reaction monitoring. We demonstrated a derivatized method suitable for the PKU screening of newborns. The recoveries for PHE and TYR were 85% and 90%, respectively. Furthermore, we compared the values of PHE and TYR in different human plasma sample storage methods, including direct plasma and dried blood spots, and the results showed no significant difference.

The areas of mass spectrometry applications seem to be much larger than those of any other analytical techniques. They extend from the determination of molecular mass in organic chemistry, through the analytical applications in forensic, environmental and omics sciences, the application in extra-terrestrial exploration and many others. Mass spectrometry, usually coupled with chromatographic techniques, has also found wide application in the pharmaceutical industry, forensic laboratories, laboratories of sanitary inspection or environmental inspection, etc. The growing areas of applications give rise to the demand for the comprehensive mass spectrometry education of undergraduates. This overview covers the body of literature describing various interesting ideas that can be successfully used for teaching mass spectrometry. Since mass spectrometry is a multidisciplinary field, old but dynamically developing, teaching mass spectrometry may be more problematic in comparison to teaching other analytical techniques, for example, there is the problem of position of mass spectrometry in the chemistry curriculum. On the other hand, it is obvious that the mass spectrometry community, besides difficult scientific work, does great and admirable teaching work, in order to perfectly educate undergraduates in the field of mass spectrometry and to make learning mass spectrometry as attractive as possible.

Atmospheric pressure field desorption (APFD) mass spectrometry (MS) has recently been introduced as a new variant of field desorption (FD) mass spectrometry. The development aimed at providing the basic characteristics of FD-MS in combination with instruments equipped with an atmospheric pressure (AP) interface. Hitherto, APFD has been demonstrated to yield both positive and negative even electron ions of highly polar or ionic compounds as well as to enable the generation of positive molecular ions, M, of polycyclic aromatic compounds. The prototype setup for APFD was based on a nano-electrospray ionization (nanoESI) source slightly modified to allow for emitter positioning in front of the AP interface of a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer. The entrance electrode of the interface was set to negative or positive high voltage with respect to the emitter at ground potential, thereby permitting the formation of positive or negative ions, respectively. This work describes a custom-built device for quicker and more reproducible sample loading on and positioning of field emitters at the entrance electrode of the atmospheric pressure interface of a mass spectrometer. In addition, the device provides means for observation of the emitter during operation and for resistive emitter heating as employed in traditional FD-MS. Emitter heating both speeds up the desorption of the analytes and allows for the desorption/ionization of analytes of higher molecular weight than without emitter heating. In some cases, the signal-to-noise ratio of APFD mass spectra is improved due to higher ion currents effected by compressing the entire process into shorter periods of spectral acquisition. The new setup enables robust and reliable operation in APFD-MS. Moreover, it has been designed as to allow for use on a range of instruments as it can either be used on an FT-ICR mass spectrometer or in combination with a trapped ion mobility-quadrupole-time-of-flight (TIMS-Q-TOF) instrument.

Lichens are recognized by their unique compounds and diverse applications in food, medicines, and cosmetics. Using ultra-high pressure liquid chromatography, coupled with a high-resolution mass spectrometer, metabolomic profiling of the lichen from a methanolic extract, was performed. Based on characteristic fragmentation patterns, twenty-five lichenic substances were tentatively identified including 5 depsides, 12 depsidones, 2 diphenyl ethers, 1 aromatic considered as possible artifact, 1 dibenzofuran, 1 carbohydrate, 1 organic acid, and 2 undefined compounds. To the best of our knowledge, this is a more complete report of their phytochemistry from . Our findings of the profile may contribute and complement the current data of the genus.

Tiotropium Bromide is a long-acting bronchodilator that is used in the treatment of chronic obstructive pulmonary disease (COPD) and asthma bronchodilator or bronchiolitis, which are substances that expand the bronchi and reduce resistance in the respiratory tract and increase airflow to the lungs. For Tiotropium Bromide found in inhaler capsules to treat COPD, determining the relevant impurities G and H, which are not UV active, is crucial. For this purpose, a new and sensitive liquid chromatography triple-quadrupole mass spectrometry (LC-MS/MS) detection with electrospray ionization by using multiple reaction monitoring in the positive mode method was developed and validated. The identity of the compounds was supported by using LC-Q/TOF. All chromatographic studies were performed with a Zorbax Eclipse XDB-C8 (150 mm x 4.6 mm, 5.0 µm) column with a total injection time of 13 min at a flow rate of 0.4 ml/min as a gradient. The limit of detection (LOD) and limit of quantitation (LOQ) in the current study range were determined as 1.0 ppb and 2.5 ppb, respectively. The results of the validation parameters following the ICH Q2(R1) guideline were determined within the acceptance criteria.

Tubulin-associated unit (tau) has an important role in the pathogenesis and the diagnosis of Alzheimer's disease (AD) and other tauopathies. In view of the diversity of tau proteoforms, antibody-free methods represent a good approach for unbiased quantification. We adapted and evaluated the single-pot, solid-phase-enhanced sample-preparation (SP3) protocol for antibody-free extraction of the tau protein in cerebro-spinal fluid (CSF) mimic and in human brain. A total of 13 non-modified peptides were quantified by high-resolution mass spectrometry (HRMS) after digestion of tau by trypsin. We significantly improved the basic SP3 protocol by carefully optimizing the organic solvents and incubation time for tau binding, as well as the digestion step for the release directly from the SP3 beads of the 13 tau peptides. These optimizations proved to be primarily beneficial for the most hydrophilic tau peptides, increasing the sequence coverage of recombinant tau. Mean recovery in CSF mimic of the 13 non-modified peptides was of 53%, with LODs ranging from 0.75 to 10 ng/mL. Next, we tested the optimized SP3 protocol on pathological tau extracted from the soluble fraction from an AD brain sample (middle frontal gyrus). We could successfully identify and quantify biologically relevant tau peptides including representative peptides of two isoforms and two phospho-peptides (pTau217 and pTau181).

In remembrance of Prof. Dr Przybylski, we are presenting a vision towards his beloved mass spectrometry (MS) and its far-reaching promises outside of the academic laboratory. Sub-atmospheric pressure (AP) ionization MS is well positioned to make a step-change in direct ionization, a concept that allows ionization and mass analyses of volatile and nonvolatile molecules from clean or dirty samples, directly, accurately, sensitively, and in a straightforward manner that has the potential to expand the field of MS into unchartered application areas. Contrary to ambient ionization MS, ionization commences in the sub-AP region of the mass spectrometer, important for practical and safety reasons, and offers , simplicity, speed, sensitivity, and robustness directly from real-world samples without cleanup. The plate source concept, presented here, provides an easy to use, rapid, and direct sample introduction from AP into the sub-AP of a mass spectrometer. Utilizing sub-AP ionization MS based on the plate source concept, small to large molecules from various environments that would be deemed too dirty for some direct MS methods are demonstrated. The new source concept can be expanded to include multiple ionization methods using the same plate source "front end" without the need to vent the mass spectrometer between the different methods, thus allowing ionization of more compounds on the same mass spectrometer for which any one ionization method may be insufficient. Examples such as fentanyl, gamma-hydroxybutyric acid, clozapine, 1-propionyllysergic acid, hydrocodone angiotensin I and II, myoglobin, and carbonic anhydrase are included.