ABSTRACT Rationale Digital (rectangular-wave) mode has emerged as an attractive alternative to conventional sinusoidal operation in quadrupole mass filters because of its simplified electronics and enhanced operational flexibility. However, the influence of geometrical imperfections on digitally driven quadrupole mass filters and the resulting consequences for ion transmission and mass resolving power remain largely unexplored. Methods The transmission characteristics of a digitally driven quadrupole mass filter operating in the first stability zone were investigated using SIMION simulations. Controlled radial asymmetry was introduced through single-rod radius variation, single-rod displacement, diagonal rod-pair radius variation, and diagonal rod-pair displacement. Stability, transmission characteristics, and resolving power were evaluated for different degrees of asymmetry and for both initial high and low states of the applied rectangular waveform. Results Radial asymmetry consistently degraded transmission efficiency and mass resolving power in all four asymmetric configurations, demonstrating the detrimental influence of geometry-induced higher order spatial harmonic field components. In addition, the performance was found to depend strongly on the initial state of the applied RF pulse, with significant changes in transmission profiles, peak widths, and resolving power. Under single-rod radius variation, the transmission peak splits for a specific initial pulse state and is correlated with a bifurcation of the stability region. Conclusions Geometrical asymmetry systematically degrades the performance of digitally driven quadrupole mass filters, while the initial pulse state introduces an additional operational parameter that influences transmission and resolving power. These findings establish practical constraints on maintaining symmetry in both rod geometry and spatial positioning, as well as on synchronizing ion injection with the driving RF pulse, and provide new insight into the interplay between higher order multipole fields and digital QMF operation.

ABSTRACT Rationale The molecular anion WF5 − constitutes an isobaric interference for the mass spectrometric detection of the HfF5 − anion. The latter is expected to form an extremely sensitive way of detecting the radionuclide 182Hf at natural levels using, for example, accelerator mass spectrometry. Methods Photoinduced detachment of WF5 − molecular anions was studied in the Double ElectroStatic Ion Ring ExpEriment (DESIREE), with the ring cooled to cryogenic temperatures (~13 K). Photon energies from 2.5 to 4.5 eV were applied using an OPO laser system for excitation. This energy range covers the threshold for the removal of an electron from that anion species. Results Photoinduced reactions were observed which indicate the existence of an energy threshold for WF5 − anions above which the neutralization yield increases strongly. In that range, the data of the neutral signal could be fitted by a linear function of photon energy E, yielding a threshold energy E th = 3.13 ± 0.01 eV. This result constitutes a substantial improvement both in the range and the resolution of the photon energy as compared to previous data and provides now a rather precise value for that threshold. Conclusions This knowledge is required for any attempts to suppress WF5 − anions by photodetachment in the ultrasensitive detection of the very rare radioisotope 182Hf using the 182HfF5 − analyte anion; for that, the 182WF5 − anion would be a stable isobaric mass interference for analyses by accelerator mass spectrometry. The radionuclide 182Hf is considered of great interest in various astrophysical environments such as nucleosynthetic processes.

ABSTRACT Introduction Ripretinib is an innovative multitargeted kinase inhibitor introduced for the treatment of advanced gastrointestinal stromal tumors, was investigated to elucidate its degradation behavior and structural transformation pathways under forced stress conditions. Although degradation studies are essential for evaluating the intrinsic stability of pharmaceutical compounds, the degradation products of ripretinib have not been comprehensively characterized. The present work focuses on LC–HRMS/MS-based structural elucidation of degradation products arising from photolytic and hydrolytic stress conditions. Methods In accordance with International Council for Harmonisation guidelines, ripretinib was subjected to acidic, alkaline, oxidative, thermal, and photolytic stress conditions. Liquid chromatography was employed to separate the degradation products, which were subsequently characterized by high-resolution tandem mass spectrometry (LC–HRMS/MS) operated in positive electrospray ionization mode. Structural assignments were established using accurate mass measurements, isotopic pattern analysis, elemental composition determination, and collision-induced dissociation pathways. Degradation kinetics under photolytic conditions were also evaluated. An in silico toxicity assessment of degradation products was performed using DEREK and SARAH prediction platforms. Results Ripretinib exhibited degradation predominantly under photolytic and hydrolytic stress conditions, leading to the formation of five degradation products. The protonated molecule of ripretinib at m/z 510 displayed a characteristic bromine isotopic distribution that facilitated differentiation between brominated and debrominated products. Hydrolytic degradation generated two products through cleavage of the urea linkage, whereas photolytic degradation produced three products involving intramolecular cyclization with concomitant debromination, hydroxylation, and N–C bond cleavage pathways. Collision-induced dissociation of protonated molecules generated diagnostic product ions that enabled structural elucidation of all degradation products. Photodegradation followed apparent first-order kinetics with a half-life of 4.2 min. One hydrolytic degradation product containing a primary aromatic amine moiety was predicted to possess mutagenic potential. Conclusion This investigation elucidates the degradation pathways of ripretinib and highlights the utility of LC–HRMS/MS in the structural characterization of degradation products generated under stress conditions.

ABSTRACT Rationale Sunlight exposure can alter plastic-associated material and generate a filterable dissolved organic matter (DOM) pool containing polymer fragments, oxygenated products, and additives. This study compared the molecular composition and time-dependent spectral differences of DOM associated with four widely used plastics. Methods Particles of poly(lactic acid) (PLA), poly(ethylene terephthalate) (PET), polyethylene (PE), and poly(butylene adipate-co-terephthalate) (PBAT) were dispersed in water and exposed to natural sunlight for 6 or 48 h. After particle removal, DOM was enriched by PPL solid-phase extraction and analyzed by negative-ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Assigned formulas were compared using elemental classes, intensity-weighted descriptors, van Krevelen distributions, Jaccard similarity, Bray–Curtis dissimilarity, and homologous-series screening. Results Between 2247 and 4661 molecular formulas were assigned per sample, with maximum absolute mass errors below 0.60 ppm. Relative to corresponding 6-h spectra, formula numbers were lower at 48 h for PLA (−37.5%) and PET (−39.3%) but higher for PE (+41.8%) and PBAT (+14.0%). Formula-set similarity was lowest for PET (Jaccard 0.329; Bray–Curtis 0.787) and highest for PBAT (0.712; 0.260). In PLA, a C3H4O2-spaced oxygen-rich series increased from 13.4% to 20.9% of the assigned intensity. A C10H8O4-spaced PET-related series contributed 8.70% at 6 h and 0.17% at 48 h. PET-48 h was dominated by CHSO formulas, whereas PE showed greater CHNO abundance and higher relative contribution of lower mass oxygenated CH2 series. PBAT retained the greatest formula-set overlap between spectra. Conclusions The 6- and 48-h spectra showed distinct polymer-dependent compositional differences. Homologous-series analysis provided information beyond van Krevelen statistics, whereas nonexclusive N- and S-containing signals highlighted the need for process blanks, dark controls, and tandem mass spectrometry before source-specific assignments. Because replicate and matched control spectra were not available in the analyzed dataset, these differences are interpreted descriptively and do not demonstrate chemical formation, disappearance, or sunlight-specific transformation.

ABSTRACT Rationale Dielectric barrier discharge ionisation (DBDI) in an active-capillary configuration (including the commercial SICRIT source) is widely used as a soft, ambient-pressure ionisation method for vapours and gases, yet the role of water vapour in controlling reagent ion chemistry and analytical behaviour has not been mechanistically described. Thus, it is necessary to understand how carrier gas humidity governs reagent ion populations and product ion formation in a DBDI source. Methods A SICRIT ion source was coupled to a triple-quadrupole mass spectrometer and operated under constant discharge conditions while switching the carrier gas between humidified and nominally dry air. Ketones and short-chain carboxylic acids were introduced at trace vapour concentrations using permeation or diffusion tubes. Reagent ion and analyte mass spectra were acquired in full-scan mode. Selected analyte ions were subjected to collision-induced dissociation (CID) to compare in-source fragments with those formed from protonated molecules. Results Under humid conditions, the reagent ion population was dominated by hydrated hydronium ions. Analytes yielded mainly protonated molecules, MH+ and their hydrates, with minimal fragmentation. Switching to a dry carrier gas reduced the total ion current by more than an order of magnitude and led to extensive, structure-dependent fragmentation. Comparison with CID spectra of MH+ indicates that the fragments observed under dry conditions arise from the fragmentation of protonated molecules rather than from the direct dissociation of radical cations. This is explained by highly exothermic proton transfer from a dominant m/z 29 reagent ion (most plausibly N2H+). Conclusions These results highlight humidity as a key operational active-capillary DBDI parameter; varying it enables both low-fragmentation ionisation in humid mode and more energetic fragmenting ionisation in dry mode. The humid mode facilitates reproducible quantitation, whereas the dry mode allows structural discrimination, exemplified by differentiation of hexanone isomers.

ABSTRACT Rationale Stable rubidium (Rb) isotopes have received increasing attention as emerging geochemical tracers for investigating planetary evolution, water–silicate interactions, and global Rb cycling. High-precision Rb isotope measurements by multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS) are commonly performed using the standard-sample bracketing (SSB) method, but this approach is sensitive to short-term instrumental drift. Methods Building upon the previously reported empirical external normalization (EEN) with 92Zr/90Zr combined with the SSB method, we adopted 88Sr/86Sr for EEN + SSB MC-ICP-MS Rb isotope measurement, owing to the closer mass discrimination between Sr and Rb. In this study, we correted the isobaric interference of 87Sr on 87Rb using an exponential law, compared Sr-EEN with Zr-EEN using the in-house USTC-Rb standard, and evaluated elemental doping effects (K, Ca, Na, and Mn). Results The results show that the USTC-Rb standard yielded δ87/85Rb values of −0.15‰ ± 0.04‰ (2SD, n = 33) by Sr-EEN and −0.16‰ ± 0.04‰ (2SD, n = 33) by Zr-EEN, indistinguishable within analytical uncertainty. Elemental doping experiments suggest that the measured Rb isotope data were not significantly affected when the K/Rb, Ca/Rb, Na/Rb, and Mn/Rb ratios were up to 100. The long-term intermediate reproducibility for NIST SRM 984 was 0.00‰ ± 0.04‰ (2SD, n = 121). Conclusions Because Sr can be effectively separated from Rb using Sr-spec resin, this Sr-EEN method provides a precise and reliable alternative for Rb isotope determination by MC-ICP-MS and exhibits high tolerance to matrix elements.

ABSTRACT Rationale The quality of analytical measurements is typically evaluated after completion of the entire, or possibly multiple, measurement batch(es). Automated, near real-time quality control (QC) during LC-HRMS acquisition can prevent reruns and sample loss by flagging issues as they occur. Functionality was evaluated by retrospective application to 5 years of river-water surveillance. Methods We present a modular MATLAB workflow that tracks isotopically labelled internal standards for peak height, retention time and mass error against rolling, method-specific expectations; applies multivariate statistical process control (MSPC; PCA with Hotelling's T 2 and SPE on intensity/retention time ratios and mass error); issues immediate email alerts; and logs outcomes to a PostgreSQL database/Grafana dashboard for trend analysis. Also, qualitative target screening via cosine-similarity MS2 checks against a local library, retention time correction, robust peak-height/noise estimation, configurable limits and automated vendor-to-open format conversion. Results In a high-voltage power-supply failure, 25/25 injections were flagged due to abnormal intensity patterns; during an organic-pump malfunction, 17/25 were flagged for retention drift up to and beyond the extraction window; and during an air-conditioning (AC) outage, MSPC detected mass error anomalies even when the ±10 ppm univariate limit was not breached. MSPC closely agreed with univariate thresholds: 95.7% of samples flagged by univariate rules were also flagged by MSPC (≈4.3% Type II), while 92.5% of MSPC-flagged samples violated at least one univariate rule (≈7.5% Type I). Conclusion These capabilities enable immediate detection, triage and documentation of performance excursions, support proactive maintenance (e.g., column aging or pump delivery issues), minimise downtime and safeguard precious samples. Although showcased on a specific LC-HRMS setup and matrix, the workflow is instrument-agnostic and broadly applicable to internal-standardised LC-HRMS methods.

Rapid Communications in Mass Spectrometry, Volume 40, Issue 14, 30 July 2026.

ABSTRACT Rationale Stable isotope-labeled compounds are indispensable internal standards for reliable liquid chromatography–mass spectrometry (LC-MS) analysis, but their preparation frequently requires multistep synthesis. Base-catalyzed hydrogen–deuterium exchange at carbon centers provides a simple alternative for generating stable isotopologues. Beyond quantitative applications, carbon-bound deuterium may serve as a mechanistic probe for investigating gas-phase fragmentation and chemically induced molecular transformations. In this work, tadalafil and omeprazole were selected as complementary model compounds to evaluate both the analytical applicability of deuterium-labeled standards and the behavior of carbon-bound deuterium during tandem mass spectrometry and acid-induced transformation. Methods Deuterium-labeled tadalafil and omeprazole were prepared by base-catalyzed hydrogen–deuterium exchange under optimized reaction conditions. The obtained isotopologue mixtures were characterized using high-resolution ESI-MS, multistage tandem mass spectrometry, 1H NMR spectroscopy, and density functional theory (DFT) calculations. Their chromatographic behavior, short-term isotope stability, and proof-of-concept applicability as LC-MS internal standards were evaluated using chromatographic comparison and analysis of post-dose human urine samples. Results Base-catalyzed hydrogen–deuterium exchange produced isotopologue mixtures dominated by tadalafil-d3 and omeprazole-d2. High-resolution mass spectrometry and 1H NMR spectroscopy consistently identified selective incorporation of carbon-bound deuterium, whereas DFT calculations explained the observed regioselectivity of the exchange. Tandem mass spectrometry of deuterated tadalafil revealed product-ion mass shifts consistent with hydrogen scrambling, demonstrating migration of carbon-bound deuterium during collision-induced dissociation and providing additional insight into the dissociation mechanism. In contrast, deuterium-labeled omeprazole retained its isotope label during acid-induced transformation. Both labeled compounds exhibited chromatographic behavior suitable for proof-of-concept LC-MS applications. Conclusions Base-catalyzed carbon hydrogen–deuterium exchange provides a rapid and cost-effective approach for preparing stable isotope-labeled tadalafil and omeprazole suitable for LC-MS applications. The study further demonstrates that carbon-bound deuterium constitutes a valuable mechanistic probe, enabling investigation of hydrogen scrambling during tandem mass spectrometry and evaluation of isotope-label stability during acid-induced molecular transformation. The combined HRMS, tandem MS, NMR, and DFT approach establishes a comprehensive framework for characterization of deuterium-labeled compounds and supports their future application in quantitative analysis as well as structural elucidation by mass spectrometry.

ABSTRACT Rationale Recent advances in ion mobility mass spectrometry (IMS) have led to the development of high-resolution platforms such as cyclic IMS and SLIM IMS (structures for lossless ion manipulations), both offering enhanced capabilities for resolving complex biomolecular conformations. Methods In this study, these two IMS technologies were evaluated for the characterization of complex natural polysaccharides, using homogalacturonan oligosaccharides (HGOS) derived from plant cell wall pectin as a model system. HGOS were generated through enzymatic depolymerization of the parent polymer and analyzed on both platforms. This approach enabled, for the first time, a direct comparison of mass spectra and ion mobility maps for identical species with varying degrees of polymerization (DP) and methylation (DM). Results As expected, single-pass analyses on the 10-m SLIM IMS provided higher resolving power, allowing a greater number of IMS features to be separated for a given species (e.g., DP5DM4) compared to single-pass cyclic IMS experiments. However, IMS features unresolved in cyclic IMS single-pass mode could be accessed through multi-pass separations. A key distinction between the platforms lies in ion formation and charge state distributions. The SLIM IMS, retrofitted to an Agilent 6560, utilizes a commercial ion source and ion optics that result in the formation of larger and higher charged species, with more cation adducts. While beneficial for resolution, this distribution can dilute signal intensity across multiple charge states, impacting sensitivity. In contrast, the cyclic IMS employs a Z-spray source that favors lower charge states, facilitating more straightforward diagnostic interpretation and characterization. Despite the superior intrinsic IMS resolution of the 10-m SLIM, the combination of ionization behavior, instrument tuning requirements, and data processing complexity makes the cyclic IMS more practical for routine analysis. Conclusions Both IMS platforms demonstrated strong capabilities for resolving HGOS structures, highlighting their complementarity and effectiveness in studying complex polysaccharide mixtures.

ABSTRACT Rationale In this work, the CCS-mass trends equation has been revisited to consider apparent changes in the ion density. Methods The ion mobility-derived collision cross section (IM-derived CCS) of negatively, single-charged Fe(II) and Fe (III) metal centers coordinated with three or four halide or linear alkyl carboxylate ligands generated by electrospray operating in the negative ionization mode were obtained using a T-wave mobility cell. Results The CCS-mass trends were fitted using the equation CCS = A × mass Pow (where A is an apparent density parameter and Pow is a shape parameter). Iron-halide complexes led to Pow parameters well below the typical limit of 0.5, which could only be explained by refining the fitting equation using a linear combination of these A and Pow parameters. Their physical meaning is described in terms of mass distribution within the volume of the iron-ligand complex ions. Conclusions The analysis of the CCS-mass trend of iron-halide and iron-carboxylate complexes allows us to predict the IM-derived CCS and the CCS-mass trends of combinations of iron-halide/carboxylate complexes. The results show no differences in trend between planar trigonal and tetrahedral geometries as described by the valence shell electron pair repulsion (VSEPR) theory.