The rapid emergence of novel psychoactive substances (NPS) presents significant analytical challenges due to their structural diversity, continuous evolution, and occurrence at trace levels in complex matrices. In this study, an analytical workflow integrating orthogonal ionization strategies based on gas chromatography coupled with high-resolution Orbitrap mass spectrometry (GC-HRMS) was developed for reliable screening, confirmation, and quantitation of selected psychoactive substances. This study demonstrates the application of combining electron ionization-based screening with positive chemical ionization-based confirmation and quantitation, enabling complementary acquisition of fragmentation and molecular ion information for improved confirmatory confidence. The GC-EI-Orbitrap approach provided high-resolution full-scan data with excellent mass accuracy (±3 ppm), enabling confident identification through accurate mass measurement, isotopic pattern fidelity, and ion ratio confirmation (±20%). The method demonstrated consistent performance for selected classes representing amphetamine-type stimulants, synthetic cathinones, and phenethylamine derivatives, with reproducible fragmentation patterns and acceptable matrix effects. Quantitative analysis using GC-CI-PRM exhibited good linearity (R2 > 0.995) over the range of 1-100 ng mL-1, with limits of detection as low as 2.5 ng mL-1. Application to spiked forensic powder matrices confirmed the robustness and reliability of the workflow. This dual-ionization GC-Orbitrap HRMS strategy enhances confirmatory capability by combining fragmentation-based identification with molecular ion preservation, providing a robust and complementary approach for the analysis of emerging NPS and demonstrating the utility of dual-ionization strategies for forensic drug analysis.
This work focuses on the extraction and analysis of polyphenols, more precisely flavonoid aglycones, from Algerian Laurus nobilis L. leaf extracts. The extraction of these bioactive substances was carried out according to a routine method with some modifications. Two main extraction steps were carried out. Hence, the first step was to solubilize flavonoids in methanol, followed by liquid-liquid extraction using ethyl acetate. The extract thus obtained was separated into six fractions by column chromatography. The identification of constituents was carried out by high-performance liquid chromatography (HPLC)-diode array detector and by comparing the ultra-violet spectra with those of standards. Accordingly, this method allowed the identification of six flavonoids among them: kaempferol, rutin, naringenin, and methoxyflavone. Moreover, these results were compared to those obtained using direct analysis in real time, time-of-flight-mass spectrometry. This convenient analytical technique not only confirmed the HPLC identification but also allowed characterization of other compounds in the bay extracts (maltol, vanillin, safrole, vanillic acid, myristicin, valerenic acid, and rhamnetin).
A series of N'-trimethylsilyl (TMS) derivatives of N,N-dialkylacetimidamides (amidines) (1-10) was investigated using gas chromatography-mass spectrometry (GC-MS) under electron ionization (EI) conditions. These amidines are of particular interest as precursors and degradation products of highly toxic Novichok nerve agents and are classified as non-scheduled reportable chemicals under the Chemical Weapons Convention (CWC) by the Organisation for the Prohibition of Chemical Weapons (OPCW). Structural elucidation and identification of the N'-TMS derivatives were achieved through comprehensive analysis of their EI fragmentation patterns. Three sets of isomeric compounds (3-5, 6-7, and 8-10) were successfully distinguished based on characteristic fragmentation pathways and the relative abundances of diagnostic ions. To further support the mass spectral interpretation, retention indices were determined for all analytes in accordance with standardized OPCW protocols. The combined use of EI-MS fragmentation data and retention indices establishes a reliable and robust analytical approach, enabling sensitive and unambiguous identification of these amidines at trace levels in complex environmental matrices following derivatization.
Electron-induced ionisation cross-sections and corresponding ionisation rate coefficients have been evaluated for the C₂F₆ molecule. Evaluated results by using the Jain-Khare semi-empirical approach of the total ionisation cross-section showing good agreement with presently available theoretical and experimental data sets. Single differential cross-sections have also been calculated for the first time at fixed incident electron energies of 100 and 200 eV. Double differential cross-sections (DDCS) have also been calculated for the first time at fixed incident electron energies of 100 and 200 eV with fixed incident angles of 30° and 60°. Three-dimensional profiles of DDCS, varying with angle and secondary electron energy, have also been generated.
Anticancer drugs are considered pseudo-persistent pollutants for the water environmental compartments due to their continuous emission into water bodies. Many sources contribute to the bioaccumulation of the drugs, and the investigation of their residues and transformation products (TPs) fate is mandatory, in particular for compounds displaying a high degree of toxicity. Here, we present a High-Performance Liquid Chromatography - High-Resolution Mass Spectrometry (HPLC-HRMS) method developed to identify and characterize the TPs of cyclophosphamide (CYC), 5-fluorouracil (5FU) and oxaliplatin (OXA), subjected to heterogenous photocatalysis mediated by titanium dioxide. The irradiation experiments were performed at different times, and the HPLC separation was achieved using a reverse-phase column. A high-resolution Orbitrap mass analyzer was used in the positive and negative ionization modes with a resolution of 30k. Tandem mass spectrometry experiments were acquired in the CID activation mode. With the developed method, we recognized and tentatively assigned the structures of six TPs for CYC, four TPs for 5FU and one TPs for OXA. The developed analytical method was then applied to real environmental water samples coming from nine sampling sites of Po River (Italy). We found the presence of CYC in four site points at level of ppb. The developed HPLC-HRMS method was a satisfactory tool to identify anticancer drugs and their TPs and to quantify them in real water environmental samples.
N-nitrosamine compounds have been recognized for their carcinogenic properties. Compounds containing secondary and tertiary amine moieties in their chemical structure, including drugs, intermediates, or solvents, are susceptible to the formation of nitrosamine impurities when they react with residual nitrite and nitrate reagents. Lidocaine (LDC) features a tertiary amine moiety, while lidocaine EP impurity E (LEE) includes a secondary amine moiety in its chemical structure. This structural characteristic makes it susceptible to the formation of N-nitroso-desethyl lidocaine (NDL) and N-nitroso lidocaine EP impurity E (NLE) during the synthesis of the LDC drug substance or the manufacturing of the LDC drug product. In this study, we developed and validated a triple quadrupole mass spectrometer (TQ-MS) method for the quantification of NDL and NLE in both the LDC drug substance and the LDC injectable formulation. This method employed a Zorbax Eclipse XDB-C18 column, utilizing an eluent composed of methanol and formic acid in water (0.1% v/v). This method enables the quantification of both NDL and NLE at a lower concentration of 0.0165 ng/mL. The method demonstrates a linear, precise, and accurate performance within the range of 0.0165 to 2.5 ng/mL for NDL and from 0.0165 to 5 ng/mL for NLE. Furthermore, the degradation pathways for both NDL and NEL impurities were discussed. In addition, the environmental impact from the TQ-MS approach using GAC tools like BAGI and AGREE was evaluated.
The stability of key Orbitrap analyzer parameters-specifically, the absence of parasitic spectral signals and the maintenance of constant ultra-high vacuum (UHV) pressure-is critically dependent on the quality of its quartz insulators. However, results from testing over 500 production units in 2025 indicate that the occurrence of disqualifying anomalies (spectral spikes and UHV pressure jumps) is not merely a function of general quartz quality but is deterministically linked to specific, localized defects introduced during assembly. A clear differentiation of root causes was established: Spectral spikes showed a statistically significant correlation (p < .001) with defects (micro-cracks, chips) on the quartz insulators of the external injection (IE) and detection (DE) electrodes, as well as on the quartz spacer ring. In contrast, UHV pressure jumps were almost exclusively (97% of cases) caused by mechanical damage and contamination on the quartz insulators of the central electrode power contact (Buchse-ZE). Critical defects on the latter included contamination and scoring from the mounting bolt, indentation marks from the spring contact, and other manufacturing micro-damage. These defects act as potent local outgassing sources. The implementation of targeted 100% optical inspection of these critical zones, supported by photographic documentation, along with modified assembly procedures, led to the practical elimination of these anomalies in a subsequent validation batch of 100 units.
Diabetes mellitus continues to be a significant worldwide health burden, necessitating safe and efficient treatment alternatives. In alloxan-induced diabetic rats, this study examined the combined antidiabetic effectiveness of chromium picolinate and Prunus persica kernel extract. Gas chromatography/mass spectrometry was used to phytochemically characterize a polyphenolic-rich extract (60% acetone). Alloxan monohydrate (140 mg/kg b.w.) was administered intraperitoneally to develop diabetes in rats. The animals were split into groups for normal control, diabetic control, chromium picolinate, Prunus kernel extract, three combination therapy groups, and conventional medication. The treatments were administered orally on a 21-day basis. Insulin levels in serum were also measured following dissection, and body weight and fasting blood glucose (FBG) were monitored prior to and after treatment. Pancreatic tissue was taken in order to determine the preservation and regeneration of B-cells through a histological analysis. Compared to individual therapy, the combined therapy had a significant benefit of reducing the level of FBG (p < .01), increasing serum insulin significantly, and rescuing the morphology of the pancreatic B-cells. These findings confirm the P. persica kernel extracts and chromium picolinate as supplementation therapies in diabetes management because they suggest that the two compounds act synergistically to enhance pancreatic protection and control glucose levels.
Polycyclic aromatic hydrocarbons (PAHs) are believed to be abundant in the dense regions of the interstellar medium (ISM) and are hypothesized to play a role in the origin of diffuse interstellar bands (DIBs). Among these, corannulene C₂₀H₁₀ stands out due to its unique bowl-shaped structure, which not only makes it an intriguing candidate for understanding interstellar chemistry but also holds potential applications in nanotechnology and materials science. To provide low-temperature laboratory benchmarks for PAH-H₂/D₂ interactions, we employed high-resolution mass spectrometry to investigate H₂/D₂ tagging of helium-doped C₂₀H₁₀ oligomers. We emphasize that the large solvation numbers accessible in helium droplets represent a model cryogenic environment and should not be interpreted as a direct prediction for the low-density ISM. H₂ tagging changes the system's stability and chemical properties, providing important information for chemistry studies. A notable peak for corannulene-monomer at 32-H₂ molecules indicates the formation of an ordered solvation layer. Theoretical studies determine that adsorption of hydrogen and deuterium on C₂₀H₁₀ clusters is enhanced by cluster size, due to enhanced bonding and electron changes such as the Highest Occupied Molecular Orbital HOMO- Lowest Unoccupied Molecular Orbital LUMO gap shrinkage. Deuterium is found with tighter bindings and smaller dipole moments, as a result of its smaller zero-point energy, with certain clusters exhibiting exceptionally robust 'magic number' structures.
Ganciclovir (GCV) is an antiviral drug used to treat cytomegalovirus infections associated with AIDS. The study of the GCV drug substance under photo-oxidation stress conditions identified five impurities. This study aims to interpret the chemical structures of the photo-oxidation products using quadrupole time-of-flight (Q-TOF) mass spectrometry. An optimized chromatographic technique employing reverse-phase high-performance liquid chromatography with photodiode array detection was used to identify the degradation products of GCV. This technique utilized an Endurus Phenyl-hexyl HP column with an eluent mixture of acetonitrile, methanol, and 1 M ammonium formate (pH 3.2). GCV's photo-oxidation products were effectively separated, achieving a resolution higher than 2.0. The Q-TOF mass spectrometry analysis characterized the five degradation products, which included 8-Oxo GCV, secondary degradation of 8-Oxo GCV, guanine, and one dehydrogenated compound. These new impurities require special attention because the drug's potency and impurity levels significantly influence the quality, safety, and effectiveness of pharmaceutical products.
A series of N,N-dialkylacetimidamides (amidines) (1-10) are designated as non-scheduled reportable chemicals under the Chemical Weapons Convention by the Organisation for the Prohibition of Chemical Weapons (OPCW). The amidines are relevant precursors and degradation products of highly toxic Novichok nerve agents. These amidines and their methyl derivatives (11-20) were systematically investigated under electron ionization (EI) mass spectral conditions. These compounds showed molecular ions with considerable abundance in their mass spectra. Each amidine was identified and characterized based on its characteristic fragmentation pattern. Among these, the possible six sets (3-5; 6 & 7; 8-10 and 13-15; 16 & 17; 18-20) of structural isomers were distinguished unambiguously using their fragmentation pattern and ion intensities. Additionally, retention indices were determined for all the analytes by following the OPCW work instructions. The combined EI mass spectral data and retention indices provide reliable identification of these amidines at trace levels in complex environmental matrices.
Reliable detection and unequivocal identification of chemical warfare agents, their precursors, and degradation products are central to verification activities under the Chemical Weapons Convention (CWC). Cyclic alkylphosphonate esters containing phosphorus-sulfur-oxygen heterocyclic frameworks are particularly underrepresented in mass spectral libraries, hindering confident identification. In this study, six CWC-relevant cyclic alkylphosphonate esters-2-alkyl-1,3,6,7,2-dioxadithiaphosphonane-2-oxides and 2-alkyl-1,3,6,8,2-dioxathiamethanphosphodane-2-oxides bearing methyl, ethyl, and isopropyl substituents were microsynthesized and systematically characterized using gas chromatography-mass spectrometry under electron ionization (EI) and positive chemical ionization (PCI) conditions. Under EI conditions, all compounds exhibited low-abundance molecular ions (2-8%) accompanied by highly reproducible and structure-specific fragmentation. Nine-membered disulfide derivatives consistently produced a dominant base peak at m/z 85, attributed to stabilized dihydrothiophene fragments, whereas methylene-bridged ten-membered analogs showed characteristic base peaks at m/z 123 or 125, reflecting enhanced ring stability. Across the series, prominent fragment ions at m/z 118 (58-70%) and alkyl-dependent ions confirmed homologous fragmentation behavior. Positive chemical ionization using isobutane generated clear protonated molecular ions ([M + H]+) at m/z 215-257 for all six compounds, enabling unambiguous molecular weight confirmation with minimal fragmentation. Gas chromatographic retention indices ranged from 1774 to 2043 and increased systematically with alkyl chain length, providing complementary chromatographic identifiers. The combined EI/PCI mass spectral fingerprints and retention index data generated in this work significantly expand reference datasets for cyclic alkylphosphonate esters and directly support reliable identification of CWC-related compounds in environmental, forensic, and Organization for Prohibition of Chemical Weapons proficiency-testing contexts.
This research introduces a model utilizing machine learning for forecasting Chemical Ionization Mass Spectrometry (CIMS) signal intensity in pesticide detection, using dibromomethane (DBrMe) as a reagent. Accurate detection of pesticides is crucial for agricultural safety and compliance. The model explores the relationship between signal intensity and ten molecular features, including molar mass, COO, N-O, N-N, N-S, C-C, S, Cl, P, and pesticide concentration in DBrMe (ppm), using algorithms like Decision Tree, AdaBoost, Random Forest, and Ensemble Learning. A dataset of 2460 samples was used for training and validation. Among the features, pesticide concentration had the strongest influence, followed by N-O, COO, and molar mass. SHAP analysis confirmed these trends, while a Leverage-based method was used to identify and remove outliers, improving model reliability. Random Forest outperformed other models, achieving the highest R2 (0.401) and lowest error. In contrast, Decision Tree and AdaBoost showed overfitting issues. Sensitivity analysis demonstrated that all variables contribute to the prediction, highlighting the model's robustness. This approach offers a cost-effective, accurate alternative to traditional experimental methods for estimating CIMS signal intensity across various pesticides and conditions, supporting faster and more efficient chemical analysis in agricultural monitoring.
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.
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-d3 and 6β-naltrexol-d3). 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.
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 10-14), along with Bis(2-methoxyethyl)sulfide (compound 8) and related disulfide Bis(2-methoxyethyl)disulfide (compound 9), 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 m/z 45 (C₂H₅O+), m/z 59 (C3H7O+), m/z 61 (C2H5S+), and m/z 75 (C3H7S+) 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).
The ion-optical properties of the second stability region (q=4.5) 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 βx and βy, 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.
Chemical modification of the tyrosine kinase inhibitor (TKI) imatinib was performed to obtain the imatinib-N-oxide, followed by metabolic profiling to study the possibilities of forming potential reactive metabolites of both imatinib and imatinib-N-oxide. The structure of the N-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-N-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-N-oxide produced two dihydroxy metabolites. Importantly, no reactive metabolites were observed for either imatinib or the imatinib-N-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 N-oxide metabolite, which is valuable information for assessing the safety and toxicological profile of this important oncology drug.
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 Celtis tetrandra Roxb. The antidiabetic activity was tested in 35 rats with diabetes induced by a single alloxan injection (140 mg·kg-1). Diabetic rats with blood glucose level (BGL >180 mg/100 mL) were treated with extracts (100 and 200 mg·kg-1) and glibenclamide (5 mg·kg-1) 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 p < 0.05 being a statistically reliable result. The ethanolic and aqueous leaf extracts of C. tetrandra (100 and 200 mg·kg-1) significantly reduced BGL, with the 200 mg·kg-1 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 C. tetrandra as an herbal remedy for hyperglycemia and maintaining a normal level of lipids.
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 18 (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 m / z 437.4 to 329.2 for ertugliflozin and from m / z 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, r 2 > 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 C max and t max values obtained were 288.28 ng/mL and 1.32 h, respectively. Authentication of the results was further done by the incurred sample reanalysis.
