European Journal of Mass Spectrometry最新文献

This article describes the key achievements over the past 10 years in the microsecond pulsed glow discharge mass spectrometry applied to the analysis of solids and gaseous mixtures. The solid-state analysis allows studying solid materials with different conductivities, including direct simultaneous quantitation of light elements with high ionization energy (N, O, F, Cl, etc.), heavy elements (U, Th, etc.), and isotope analysis. Dielectric materials analysis is considered in details with special emphasis on sample preparation approaches. Particular attention is focused on a new application of the technique for detection of volatile organic and inorganic compounds in gas mixtures (model gas mixtures, ambient air and exhaled air). This approach has prospects for solving medical and environmental problems as well as for process gas monitoring. Several applications (He determination in deuterium, detection of VOCs, Xe and other inorganic compounds in air) are presented as examples. Using the high resolution (6000 for Pb, m/z 208) of Lumas PGD-301 time-of-flight mass spectrometer helps to eliminate most of the interferences and thereby improves the analytical performance. Combination of high energy electron ionization with soft Penning and other ionization mechanisms allows to detect almost all known elements and molecules.

Rimegepant is a calcitonin gene-related peptide receptor antagonist that has been licensed for migraine headache treatment in the United States, the European Union, the United Kingdom, Hong Kong, Australia, and Kuwait. The oxidation stress study of the Rimegepant drug substance revealed the presence of five impurities. Rimegepant degraded by 5% under the selected oxidation conditions, meeting regulatory expectations. Four out of five impurities are enhanced by more than 1%. This research aims to characterize these oxidation degradation products utilizing the triple quadrupole mass spectroscopic technique. The Rimegepant oxidation degradation products were identified using an optimized chromatographic method that relies on reverse-phase HPLC with PDA detection. This technique utilized a Waters Xbridge C18 column with an eluent mixture of acetonitrile and 0.1% formic acid in water. The oxidation products of Rimegepant have been effectively separated, with a resolution above 3.0. Triple quadrupole mass spectrometry analysis characterized the five degradation products, which showed three N-oxide impurities with masses m/z 566, m/z 550, and m/z 548, as well as two hydrolysis products with masses, m/z 218, m/z 290. These new impurities deserve special attention because the drug's potency and related impurity levels determine any pharmaceutical medication product's quality, safety, and effectiveness.

In 2018, the Food and Drug Administration and the European Medicines Agency identified nitrosamine impurities in certain drugs, prompting detailed investigations by international regulatory authorities. According to ICH M7 (R1) guidelines, nitrosamines are classified as Class 1 substances, the most hazardous category, based on their carcinogenic and mutagenic properties. They are also recognized as probable human carcinogens by the International Agency for Research on Cancer. Since nitrosamine-induced DNA damage poses significant health risks, identifying potential nitrosamines in pharmaceutical products is crucial. In this study, a simple and efficient extraction method was designed to minimize matrix effects. These effects were evaluated using calibration curves prepared for each drug product in their respective matrices. The developed method was performed using an Agilent 1260 series HPLC system and an Agilent 6460 triple quadrupole tandem mass spectrometer. An Inertsil ODS-3 C18 (5 µm, 4.6 × 150 mm) column was employed for chromatographic separation. A triple quadrupole mass detector with electrospray ionization was used for detection, and multiple reaction monitoring was employed for quantification. The correlation coefficients (r²) were at least 0.999 for all eight nitrosamines. Limit of detection and limit of quantification values were determined as 0.05-0.8 ng/mL and 0.1-2.0 ng/mL, respectively. Validation results demonstrated satisfactory selectivity, accuracy, precision, and stability. The results demonstrated that the developed method is capable of reliably detecting potential nitrosamines present in pharmaceutical products at trace levels. This method contributes significantly to pharmaceutical safety and can serve as a valuable tool for future analyses.

Background: Orofacial pain, encompassing a broad spectrum of conditions, arises from the intricate interplay of sensory, cognitive, and emotional components. Accurate diagnosis and management are challenging due to the complexity of orofacial anatomy. Saliva, a non-invasive diagnostic fluid, offers significant potential for identifying biomarkers associated with pain and systemic diseases. Objective: This study aims to investigate the salivary proteome profile in individuals with orofacial pain to identify potential biomarkers for improved diagnostic accuracy and therapeutic interventions. Methods: Saliva samples were collected and processed from individuals experiencing orofacial pain. Proteomic profiling was conducted using advanced mass spectrometry techniques. Identified proteins and metabolites were analyzed to determine their relevance to immune responses, inflammation, and metabolic pathways. Statistical evaluations were performed to identify significant differences in biomarker expression. Results: Key immune-related proteins, such as immunoglobulin A (360.7075 m/z) and lysozyme C (315.8543 m/z), were identified, highlighting their roles in mucosal immunity and antimicrobial defense. Essential amino acids, including leucine (207.1007 m/z) and tyrosine (126.9058 m/z), emphasized their importance in protein synthesis and metabolic pathways. Lipid metabolites like deoxycholic acid (259.8098 m/z) and linoleic acid (183.9124 m/z) suggested active lipid metabolism. Elevated uric acid levels (248.9720 m/z) indicated oxidative stress and chronic inflammation. Conclusion: Saliva's proteomic profile provides valuable insights into the mechanisms underlying orofacial pain. Identified biomarkers have potential applications in diagnostics and personalized therapeutic strategies. Future studies should focus on validating these findings in larger cohorts to enhance clinical applicability.

The stability regions formed by the asymmetric sinusoidal shape of the periodic supply potential of the quadrupole mass filter are calculated, with the signal duty cycle $d=0.5$. Two cases are considered, when $A_1<A_2$ and $A_1>A_2$, where $A_1$ and $A_2$ are the amplitudes of the positive and negative parts of the sinusoid. Stability islands are revealed, where the QMF operation is possible by changing amplitude $A_2$ without DC potential. For the values $A_1=1$ and $A_2=0.8$, the mass selected instability mode with a resolution of about 7000 is found. In this island, the potential well depth reaches its maximum along the Y coordinate. At the amplitudes $A_1=1$ and $A_2=1.8-2.0$, stability regions are formed, the operation in which allows reaching $R_{0.5}=2000$. The results of the transmission and excitation contours modeling confirm the validity of the method for calculating the stability diagrams of a linear quadrupole with asymmetric sinusoidal waveform.

Phthalate esters, frequently used as plasticizers in consumer products, raise concerns because of potential health effects. Using density functional theory (DFT) with B₃LYP 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 H₃O${}^{+}$, NH${}_4^{+}$, NO${}^{+}$ and O${}_2^{+}{}^{\bullet }$ 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${}_{\mathrm{cm}}$ = 0.28 eV. SIFT-MS rates diminish with rising temperature. The high kinetic energy data of H₃O${}^{+}$, NO${}^{+}$ and O${}_2^{+}{}^{\bullet }$ 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${}_4^{+}$ ions indicates their suitability for quantifying phthalate esters using NH${}_4^{+}$-CI-MS techniques.

The dimer and trimer structures of the non-amyloidogenic rat islet amyloid polypeptide 21-37 peptide, formed in an H₂O/CH₃OH (1% CH₃COOH) 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 L₇ and P₈ 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 (u = 3-4, 6-7, 12) or y_n (n = 10-11, 13-14) in the [Mono + 2H]²⁺ (=[monomer + 2H]²⁺) tandem mass spectrum. MS/MS analysis of the [Di + 3H]³⁺ (=[dimer + 3H]³⁺) complex indicated that [Di + 3H]³⁺ comprised [Mono + H]¹⁺ and [Mono + 2H]²⁺ subunits. During covalent bond dissociation of the [Di + 3H]³⁺ complex, a fragmentation pattern was observed in the form of {mono + (fragment ion of [Mono + 2H]²⁺)}, resulting from the collision energy dissociation of the [Mono + 2H]²⁺ peptide. The [(C-terminal)-(C-terminal)] interaction geometry was proposed for the [Di + 3H]³⁺ complex based on the observation of [y₁₀+ y_n]²⁺ (n = 10-11, 13-16) fragment ions in the [Di + 3H]³⁺ tandem mass spectrum. MS/MS analysis of the [Tri + 4H]⁴⁺ (=[trimer + 4H]⁴⁺) complex indicated that [Tri + 4H]⁴⁺ comprised [Mono + H]¹⁺ and [Di + 3H]³⁺ subunits. The (monomer-[Di + 3H]³⁺)⁴⁺ complex geometry was assumed to be stable based on the presence of {mono + (fragment ion of [Di + 3H]³⁺)} ions in the tandem mass spectrum of the [Tri + 4H]⁴⁺ complex. The two [Mono + (y₁₀+ y₁₀)]²⁺ and [Mono + (Mono + y₁₀)]³⁺ fragment ions also supported the (monomer-[Di + 3H]³⁺)⁴⁺ complex geometries of the [Tri + 4H]⁴⁺ complex. The [(C-terminal)-(C-terminal)] interaction geometry of the [Di + 3H]³⁺ subunit is thought to be conserved in the [Tri + 4H]⁴⁺ complex geometries.

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 1-4 and also to shed light on the gelation processes. By inspecting the gelation of several solvents, we showed that 1 (R, R) 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 1 (R, R) is a good gelator due to favorable intramolecular interactions that remain preserved in the gas phase. Compound 3 (meso) 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.

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 $-2/3$ 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.

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.