Chemical modification of the tyrosine kinase inhibitor (TKI) imatinib was performed to obtain the imatinib--oxide, followed by metabolic profiling to study the possibilities of forming potential reactive metabolites of both imatinib and imatinib--oxide. The structure of the -oxide metabolite was elucidated using various spectrometric techniques, including mass spectrometry, and nuclear magnetic resonance analysis. Metabolic profiling and the potential for reactive metabolite formation were investigated for both imatinib and the synthesized imatinib--oxide using rat liver microsomes and three chemical trapping agents (potassium cyanide, methoxylamine, and glutathione). Identification and characterization of the metabolites and any reactive metabolites were performed using an Agilent 6320 ion trap mass spectrometer. The results showed that imatinib--oxide produced two dihydroxy metabolites. Importantly, no reactive metabolites were observed for either imatinib or the imatinib--oxide in the presence of the chemical trapping agents. These findings contribute to the understanding of the metabolic fate and reactive metabolite potential of the TKI imatinib and its -oxide metabolite, which is valuable information for assessing the safety and toxicological profile of this important oncology drug.

Naltrexone, an FDA-approved mu-opioid receptor antagonist for alcohol dependence, requires therapeutic drug monitoring due to its pharmacokinetic variability. This study developed a liquid chromatography-electrospray ionization-tandem mass spectrometry method for accurately quantifying naltrexone and its active metabolite, 6β-naltrexol, using deuterated internal standards (naltrexone-d and 6β-naltrexol-d). Sample preparation involved solid-phase extraction with a Strata-X cartridge followed by elution. Separation was performed on a C18 column with gradient elution at 0.3 mL/min. Detection in dynamic multiple reaction monitoring mode used ion transitions at m/z 342 > 324 for naltrexone and m/z 344 > 161 for 6β-naltrexol. The calibration curves were linear over the range of 0.0152-33.3 ng/mL for naltrexone and 0.410-100. ng/mL for 6β-naltrexol, both with a correlation coefficient of 1.0000 and 0.9998, individually. Intraday and interday variations were below 9.2% for naltrexone and 6.6% for 6β-naltrexol. The recovery was 99.5% for naltrexone and 95.0% for 6β-naltrexol. Applied to plasma samples from five patients receiving 50 mg oral naltrexone daily for 12 weeks, average concentrations were 3.30 ± 4.40 ng/mL (naltrexone) and 48.5 ± 23.4 ng/mL (6β-naltrexol). The developed assay method effectively quantifies naltrexone and its metabolite in alcohol-dependent patients in Taiwan.

Diabetes mellitus (DM) is an onset metabolic illness in which hyperglycemia occurs due to acquired or inherited impaired insulin production and ineffective action. Diabetes is frequently managed with the use of drugs, which may have adverse consequences even though they are good at regulating blood glucose levels. Herbal remedies are therefore being investigated as a substitute because of their reduced toxicity and fewer adverse effects. Using alloxan-induced diabetic rats, this work intends to investigate the possible anti-diabetic and anti-hyperlipidemic effects of ethanolic and aqueous leaf extracts of Roxb. The antidiabetic activity was tested in 35 rats with diabetes induced by a single alloxan injection (140 mg·kg). Diabetic rats with blood glucose level (BGL >180 mg/100 mL) were treated with extracts (100 and 200 mg·kg) and glibenclamide (5 mg·kg) as a standard drug, and fasting BGL, lipid profiles, body weight, and pancreatic histopathology were assessed. The result was analyzed using SPSS software by one-way ANOVA, followed by Tukey's post hoc test, with  < 0.05 being a statistically reliable result. The ethanolic and aqueous leaf extracts of (100 and 200 mg·kg) significantly reduced BGL, with the 200 mg·kg ethanolic extract showing the most notable effect at day 21st. Lipid profiles improved, and pancreatic histopathology revealed increased β-cell regeneration. The preliminary study supported the use of leaf extracts from as an herbal remedy for hyperglycemia and maintaining a normal level of lipids.

The ion-optical properties of the second stability region () formed by the square wave shape potential with a duty cycle of 50% are studied as applied to the operation of a linear ion trap. The stability diagram is presented in detail, the stability parameters and , which determine the spectrum of ion oscillations, are calculated; the pseudopotential well-depth for this zone is given. The LIT acceptances for sinusoidal and rectangular wave forms are shown for comparison. Based on the obtained data, the excitation contour is modeled using the trajectory method, where a resolution of 25,000 without using gas damping is found.

Sulfur mustard, a Schedule 1 chemical under the Chemical Weapons Convention (CWC), poses a significant threat to human health, animals, plants, and the environment due to its persistent nature. Bis(2-methoxyethylthio)alkanes (compounds -), along with Bis(2-methoxyethyl)sulfide (compound ) and related disulfide Bis(2-methoxyethyl)disulfide (compound ), were synthesized and investigated using gas chromatography-mass spectrometry (GC-MS) under both electron ionization (EI) and positive chemical ionization (PCI) conditions. These compounds are structurally analogous to known degradation products of sulfur mustard, such as thiodiglycol and its derivatives, making them of particular interest for environmental analysis and chemical forensics. EI mass spectra revealed consistent fragmentation behavior, including α cleavage and neutral losses. Diagnostic ions at / 45 (C₂H₅O), / 59 (CHO), / 61 (CHS), and / 75 (CHS) were observed across the series. A generalized fragmentation pathway is proposed to support structural elucidation and homologous trend interpretation. PCI with isobutane and ammonia provided molecular ion confirmation via [M+H], [M+39], and [M+18] adducts. Due to their chemical resemblance to vesicant degradation products, these sulfur-containing compounds, along with their comprehensive mass spectral data, contribute to the spectral libraries essential for off-site analysis, substance verification, and participation in official proficiency tests conducted under the framework of the CWC by the Organization for the Prohibition of Chemical Weapons (OPCW).

In this study, an analytical approximation that can be used to estimate the change in the electric field caused by the introduction of circular slits on endcap electrodes of toroidal ion trap mass analysers will be developed. A theory has been developed to estimate the contribution of circular slits on the electrodes of a toroidal ion trap. In this theory, the first potential due to an arbitrary aperture on an infinite ground plane will be derived. This will be specialised to obtain potential due to a circular slit on an infinite ground plane. The potential due to a circular slit on an infinite ground plane will be used to evaluate the field within the toroidal traps having circular slits. The approximation developed in this paper has been verified on two arbitrarily selected toroidal traps. One of these arbitrary traps has circular-shaped electrodes, and the other trap has asymmetric hyperbolic-shaped electrodes. Fields estimated by this approximation agree well with those obtained using the boundary element method. Additionally, the study reveals an interesting correlation between the secular frequency of ion motion and the width of the circular slit. The secular frequency reduces as the slit width is increased. The reduction in secular frequency is proportional to the square of the slit width.

Cross-linking mass spectrometry is rapidly becoming a choice method for determining a protein's higher-order structure as well as capturing inter-protein interactions. In particular, diazirene-based photo-activatable cross-linkers, such as sulfo-SDA have been shown to be effective at generating high-density cross-linking data. Previously, we have shown that this method may be used to study binding orientation between two non-covalently linked complexes; however, several unexpected ions were noted in the MS2 spectra. In this study, the tandem mass spectrometry fragmentation patterns of sulfo-SDA-initiated cross-linked peptides under higher-energy collision induced (HCD), collision induced (CID) and electron transfer with supplementary HCD (EThcD) dissociations are discussed. The analysis revealed substantial insights into localising cross-linking sites, which is essential for accurate determination of protein higher-order structural characteristics.

The nominal mass of amino acid residues calculated from their elemental compositions are defined by prime numbers far more often than chance, and such residues appear to play an important role in the formation and biology of proteins. It is proposed therefore that consideration be given to classifying prime mass amino acids as such, beyond the more common, familiar definitions associated with the other physicochemical properties of amino acids including charged or non-charged, hydrophobic or hydrophilic, polar or non-polar, acidic or basic, aliphatic or aromatic. Greater focus could also be given to such residues during peptide and protein sequencing with mass spectrometry and the construction of structural maps, given their predominantly hydrophobic character and thus their role in protein folding and transmembrane domains. The use of prime numbers to define amino acids based on the sum of the atomic masses from their elemental compositions invokes other recent interest and observations whereby prime numbers were organised in a way that mirrors electrons arranged within the orbitals of an atom. The article links number theory with both the physical and biological sciences, and mass spectrometry, for the first time.

Carboxylic acids containing an -acetyl substituent were studied using tandem mass spectrometry (MS/MS). Decarboxylation was observed for deprotonated -acetylmandelic acid, whereas deprotonated acetoxyacetic acid and acetylsalicylic acid fragmented by two competing pathways. In the lower energy process, the product ion was formed by intramolecular proton abstraction and subsequent neutral loss of ketene (CH=C=O) from the -acetyl group. At higher collision energies, nucleophilic displacement of the -acetyl group by the carboxylate group of acetoxyacetate yielded acetate (CHCO) as the more abundant product ion. The relative energetics computed for the reaction pathways of acetoxyacetate were consistent with the product ion spectra. Overall, the observation of both the loss of ketene and the formation of acetate ion are characteristic of an -acetyl group in the precursor carboxylate ion undergoing collision-induced dissociation. The different fragmentation behavior exhibited by -acetyl mandelate was attributed to the charge stabilizing properties of the phenyl substituent that facilitated decarboxylation. Thus, the fragmentation processes observed depended on the structures of the -acetyl-substituted carboxylate ions and the associated intramolecular interactions.

In this paper, we develop and describe a technology for delivering micro- and nanoparticles from solutions into a linear quadrupole Paul trap using the paper spray method. The developed technology is based on electrospraying of colloids with the particles from paper cartridges into the electrodynamic trap. The proposed method has been experimentally verified using a colloid solution of AgInS/ZnS quantum dots in toluene. It has been shown that electrospraying of the solution from a paper cartridge is observed when applying a DC voltage in the range of 5-12 kV. Stable retention of the delivered particles in the trap is observed when applying an AC voltage with a frequency of 500 Hz and an amplitude of 1000 V on the power trap electrodes and DC voltage 60-290 V on the end-cap electrode. The features of the developed technology are described in detail.

The stability of gas-phase clusters primarily depends on their size, with magic numbers exhibiting exceptional conformal stability due to symmetric or closed-shell configurations. This phase is ideal for analyzing intrinsic properties, that is, as cluster size increases, their behavior transitions from molecular to bulk-like. The characterization of these clusters has been facilitated by advancements in mass spectrometry, which has also played a crucial role in revealing the existence of magic numbers. In this study, helium nanodroplets-doped fullerenes C are electron-impact ionized along with dialane Al2H6 using high-resolution mass spectrometry to analyze various abundance distributions, revealing significant local irregularities (anomalies). Mass spectra of dialane-tagged C, that is, [C][AlH], display anomalies at  = 4 and  = 8 across nearly all C cluster sizes, indicating localized irregularities. Peaks other than these magic numbers exhibit antimagic behavior. These results highlight specific mass-to-charge ratios in cationic clusters, advancing our comprehension of these complex molecules and their potential applications in nanotechnology and chemistry.

The adsorption and surface ionization of cocaine molecules CHNO (: 303 Da) on the surface of oxidized tungsten was studied using the non-stationary voltage modulation method in a high-vacuum mass spectrometric setup employing a "black chamber," all the walls of which are cooled with liquid nitrogen. The activation energy and of thermal desorption were determined, as well as pre-exponential factors in the continuity equation for the radicals CHON and CHON ( 182) during the dissociation of cocaine molecules with a break () bonds with the formation of desorbing radicals by surface ionization on the surface of oxidized tungsten WO. The results of determining the coefficient of surface ionization, the heat of sublimation, and assessing the ionization potentials of these radicals are presented, and also determined from thermal desorption spectra of the activation energy of thermal desorption of the resulting ions in the air atmosphere.

A high-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantification of ertugliflozin in human plasma, employing ertugliflozin D5 as the internal standard. Methyl tertiary butyl ether-based liquid-liquid extraction technique was employed, followed by chromatographic separation on Kromasil-C (100 × 4.6 mm, 5 µm) column using a mixture of methanol and 10 mM ammonium formate buffer (80:20, v/v) as the mobile phase at a flow rate of 1 mL/min. The mass transitions were observed from / 437.4 to 329.2 for ertugliflozin and from / 442.2 to 334.3 for ertugliflozin D5 by multiple reaction monitoring in a positive ion electro spray ionization source. The linearity was established in the concentration range of 1-500 ng/mL, with the correlation coefficient,   0.99. Validation of the method was performed as per US FDA guidelines, and the results were found well within the acceptance limits. The method was applied successfully for the pharmacokinetic study of ertugliflozin 15 mg after a single oral dose under fasting conditions in healthy male volunteers. The and values obtained were 288.28 ng/mL and 1.32 h, respectively. Authentication of the results was further done by the incurred sample reanalysis.

Characterization of impurities is very important in drug chemistry and process development. Due to these transformation products (TPs), the drug may lose its stability, safety and efficiency. Hence, it is imperative to develop a selective analytical method enabling chromatographic separation of drug and their TPs. Glycopyrronium bromide is a quaternary ammonium drug that acts as an anticholinergic agent and is used to treat chronic obstructive pulmonary disease. Glycopyrronium bromide was forced to degrade under various conditions, according to the International Council for Harmonisation Q1A (R2) guidelines. The resulting TPs were further separated on an Accucore C18 (150 × 4.6 mm, 2.6 μm) column using a gradient program. Glycopyrronium bromide yielded two TPs under acid and base hydrolytic stress conditions. Structural characterization of both TP1 and TP2 was carried out by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in combination with HRMS. Further, the TPs were isolated using semi-preparative HPLC, and their structures were confirmed by H and C NMR spectroscopy. toxicity studies of isolated TPs were carried out using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay method and they were found non-toxic.

The rapid increase in incidences of antibiotic resistance, as well as the severity of side effects associated with the synthetic drugs, have directed the researchers to focus on the natural reservoirs as an alternative to the available drugs. The aim of this study was to evaluate the antimicrobial, anti-inflammatory, cytotoxicity assay, and gas chromatography-mass spectrometry (GC-MS) profiling potential of leaf extracts. Aqueous and ethanolic extract of the leaf was prepared by the maceration process. The anti-microbial potential by disc diffusion method was estimated against , , , and Ethanolic extract was more effective with the zone of inhibition of 18.32 ± 0.012 mm and 12.97 ± 0.02 mm against and , respectively. Aqueous extract did not show any results against and . Cytotoxicity assay on Vero cells assured the safety of the extract with IC 920.45 μg/mL. In vivo anti-inflammatory potential was evaluated by the carrageenan-induced rat paw edema. Edema size was measured by digital Vernier caliper. The maximum paw inhibition (40.4%) was observed in the group treated with 500 mg/kg of ethanolic extract. There was a significant decrease in the level of inflammatory biomarkers such as C-reactive protein and interleukin-6, and hematological parameters. GC-MS of ethanolic extract identified the six major bioactive compound classes, including phytol, aliphatic alcohol, flavonol, sterols, and triterpenes.

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.

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 . Two cases are considered, when and , where and 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 without DC potential. For the values and , 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 coordinate. At the amplitudes and , stability regions are formed, the operation in which allows reaching . 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.

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. 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. 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. 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. 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.

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.

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 / 566, / 550, and / 548, as well as two hydrolysis products with masses, / 218, / 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.

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, / 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.