Professor Jean-François Muller, a distinguished figure in the field of mass spectrometry, made significant contributions to the advancement of analytical chemistry and its applications. As the founding director of the Laboratory of Mass Spectrometry and Laser Chemistry at the University of Metz, JF Muller played a pivotal role in establishing Metz as a leading centre for mass spectrometry research. His pioneering work, particularly in the development of matrix-assisted laser desorption/ionization (MALDI) instrumentation and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FTICR MS), has had a profound impact on various scientific disciplines. This article commemorates Pr. JF Muller’s illustrious career and highlights his collaborative efforts with industrial partners such as TOTAL, which led to groundbreaking advancements in MS analysis. I will delve into the key findings of my thesis which focused on instrumental developments for MALDI analysis and imaging, as well as personal reminiscences and the impact of his inspiring mentorship.

RATIONALE: Collisional cross sections (CCS) are an important characteristic of gas-phase ions that are measured using ion mobility-mass spectrometry (IMS). Typically, CCS measurements are performed with drift-tube IMS or travelling-wave IMS. However. in a high-field asymmetric waveform ion mobility (FAIMS) device, the non-linear path through the device makes CCS determination more challenging. This research explores whether CCS can be predicted using a microscale FAIMS by using known CCS standards. METHODS: An Owlstone ultraFAIMS microscale FAIMS spectrometer was coupled to an Orbitrap Exactive mass spectrometer. 2 different CCS standard mixtures (tetraalkylammonium halides and poly-DL-alanine oligomers) were used to evaluate the systems potential to predict CCS. Test peptides bradykinin acetate and substance P were used to determine prediction accuracy for singly and doubly charged peptide species using external calibration with a series of poly-DL-alanine peptides for +1, +2 charge states. RESULTS: Calibrations with excellent correlation coefficients (R 2 = 0.99) for both TAAHs and poly-DL-alanine were obtained. Good predictive accuracy was achieved for bradykinin [M+2H] 2+ with a ±0.5% difference between experimental and published CCS at a dispersion field strength (DF) of 250 Td, the model proved less accurate for bradykinin [M+H] + (±1.4% at 240 Td). The prediction accuracy for the [M+H] + and [M+2H] 2+ ions of substance P was within ±5% and ±3% at 250 Td respectively, while at higher DF values accuracy decreased to approximately 5%. CONCLUSIONS: Distinct relationships were observed between CCS and transmission CF with both calibrants. Optimum predictive performance was obtained at DF strengths of 240-260 Td. At lower DF accuracy is reduced by insufficient resolution of analyte ions from solvent cluster adducts while at higher DF values, poor transmission becomes a factor. Nevertheless, these data suggest microscale FAIMS can conduct CCS measurements with reasonable accuracy when the compound being measured has similar structural features to the CCS standards used.

not-yet-known not-yet-known not-yet-known unknown Born on June 1, 1940, in Lyon, Jean-François Muller studied in Autun before entering the Collège Stanislas in Paris and obtaining an engineering degree from the Strasbourg Higher National School of Chemistry (ENSCS), where he met his wife, Daniel. After graduating in 1965, he joined the Faculty of Science at the University of Metz at its foundation in 1970, as an Assistant Professor of Organic Chemistry. There, he prepared his doctorate in physical sciences, focusing on peri-series cyclisation of naphthalenic and benzo(b)thiophenic compounds (doctorat es-science of physics, 1973). After a first post-doctorate in chemistry-physics at the University of Basel (Switzerland) (1974-1975) and a second one in photochemistry at the University of Utah (USA) (1976-1977), he has specialised and became involved in the development of mass spectrometry in France.

Rationale. Data are required for SIFT-MS analysis of per- and poly-fluoroalkyl substances (PFAS) that are persistent in the environment and cause adverse health effects. Specifically, the rate coefficients and product ion branching ratios of the reactions of H 3O +, NO +, O 2 +•, O -•, OH -, O 2 -•, NO 2 -, and NO 3 - with PFAS vapours are needed. Methods The dual polarity SIFT-MS instrument (Voice200) was used to generate these 8 reagent ions and inject them into the flow tube with N 2 carrier gas at a temperature of 393 K. Vapours of pentafluoropropionic acid, heptafluorobutyric acid, nonafluoro-1-hexanol, perfluoro-2-methyl-2-pentene, perfluorohexanoic acid, perfluoro(2-methyl-3-oxahexanoic) acid, tridecafluoro-1-octanol, and nonafluorobutane-1-sulfonic acid were introduced in dry and humid air. Full-scan mass spectra were collected for all reagents at variable PFAS concentrations and analysed numerically. Results Rate coefficients were determined for 64 reactions, for which 55 positive and 71 negative product ions were identified. The branching ratios for the primary reaction channels were extracted from the data, and the secondary chemistry with H 2O molecules was qualitatively assessed. The thermochemical data were calculated for the H 3O + reactions using Density Functional Theory (DFT). Conclusions An important observation is that secondary reactions with water molecules remove the positive product ions, making them unsuitable for practical SIFT-MS analysis of PFAS vapours. In contrast, most negative reaction product ions are not significantly affected by humidity and are thus preferred for the SIFT-MS analyses of PFAS substances in various gaseous matrices.

Atmospheric Pressure Solids Analysis Probe (ASAP) Mass Spectrometry was used for the rapid analysis of 250 synthetic opioid standards, including 210 fentanyl analogs of similar molecular weight and structure, 32 non-fentanyl related opioids, and 8 fentanyl precursors. Using four cone voltages (5, 15, 35 and 50 V) both precursor and product ion mass information was obtained for all standards. The accumulated spectral data was used to build a spectral library, which was utilized to create and validate a statistical model via LiveID software. To assess the accuracy of the database, 5 blind and 4 dirty cook fentanyl samples were analyzed. Using LiveID, obtained data for each sample was processed and matched against all compounds in the spectral library to produce matching scores that ranged from 0- 999. For all samples, the correct identity of each fentanyl analog was ranked within a score of 800 -997. Thus, proving that ASAP, when used alongside a real-time sample recognition software, such as LiveID, can help conduct presumptive testing for fentanyl and fentanyl analogs in blind and dirty samples, making it a promising alternative to some of the most commonly used analytical screening techniques.

Sourcing in chemical forensic science refers to the attribution of a sample to a specific source using a characteristic signature. It relies on the identification of chemical attribution signatures (CAS), including chemical markers such as residual synthetic precursors, impurities, reaction by-products and degradation products, or even metabolites. Undertaking CAS for chemical threat agents (CTA) can be used to provide an evidentiary link between the use of a given chemical and its precursor(s) to support forensic investigations. Organophosphorus compounds, a class of nerve agents can be produced by different, more or less complex synthesis routes that can lead to specific CAS. Chlorpyrifos (CPF), an organophosphorus pesticide was selected as model compound. To assess the specificity of impurity markers originated from a chemical synthesis, untargeted fingerprints of crude CPF from different synthesis pathways were analyzed as a first use-case using metabolomics-based trace discovery strategies. Seven different CPF synthesis routes were considered and their crude mixtures were analyzed with a minimal sample preparation. Analyses were performed on a trapped ion mobility spectrometry (TIMS) coupled to liquid chromatography (LC) and high-resolution mass spectrometry (HRMS). Chemometrics analyses were conducted with multivariate methods to extract discriminating features (i.e. relevant impurities), annotate and identify them. Then, unknown samples were analyzed in blind conditions without any information of the synthesis pathway employed. The aim is to validate the methodology seeking some discriminating impurities identified in the first section to attribute and classify them according to the synthesis route.

Alkali metals have been used to degrade SF 6 in liquid ammonia. The products include metal fluorides. In this study, we reacted K − and Ag − with SF 6 in a triple quadrupole mass spectrometer. The atomic metal anions were formed by in-source collision-induced dissociation (CID) of their respective oxalate salts as previously described by our group. The only two reaction products observed were SF 6 − and SF 5 −. At low collision energy, the latter was deduced to be formed via an abstraction by the metal of F from SF 6 − formed by electron transfer in the encounter complex between the metal anion and neutral SF 6. As the collision energy was increased, there was evidence of a CID contribution to SF 5 − directly from SF 6 −.

The unimolecular reactions of protonated α- and β-pinene ions were explored with a combination of collision-induced dissociation tandem mass spectrometry and theory. The two main dissociation reactions in each ion lead to the losses of neutral propene and isobutene. The difference observed between the two ions is a greater relative abundance of propene loss in the case of protonated a-pinene. Both ions were found to dissociate over the same minimum energy reaction pathway, the only difference being the site of initial protonation in the two ions. a-Pinene preferentially protonates at the bridging carbon, while b-pinene can only significantly protonate at the exocyclic double bond. This leads to a lower appearance energy for loss of isobutene, and thus relatively greater m/z 81 fragment ion abundance for b-pinene.

The complexation of mercury (Hg) with dissolved organic matter (DOM) is a pivotal factor influencing transformations, transport, and bioavailability of Hg in aquatic environments. However, identifying these complexes poses a significant challenge because of their exceedingly low concentrations and presence of coexisting ions. In this study, mercury-dissolved organic matter (Hg-DOM) complexes were isolated through solid phase extraction (SPE) from Hg-humic acid suspensions and complexes were putatively identified using ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Dissolved organic carbon (DOC) and total Hg analysis before and after SPE showed an increase in DOC:Hg ratio. The DOC:Hg ratio was lower in extracts from cartridges with silica structure bonded with hydrocarbon chains (C18) than priority pollutant cartridges (PPL) cartridges at circumneutral pH, indicating that C18 was more effective at extracting DOM complexed Hg. These results were confirmed with FTICR-MS analysis, where two Hg-DOM complexes were putatively identified from PPL extracts as opposed to nine from C18 (Winnow score >75%). In addition, C 8H 13HgN 2O 2S, a molecular formula with a m/z ratio of 403.04, was identified across three separate extractions using a C18 cartridge, suggesting that the complexes were preserved during extraction and, presumably, electrospray ionization. These results highlight the effectiveness of the methodology developed in this study - SPE coupled with FTICR-MS for isolating and identifying Hg-DOM complexes. This approach allows for the exploration of the elemental and structural composition of Hg-DOM complexes, which affects Hg speciation, bioavailability, and transformations in aquatic ecosystems.

RATIONALE: Understanding plant defense mechanisms against pathogens is critical for agricultural productivity and crop protection. This study focuses on the quantification of camalexin and scopoletin, essential phytoalexins in Arabidopsis thaliana, using advanced mass spectrometry techniques. Accurate measurement of these compounds can provide insights into plant resistance and support agricultural research. METHODS: Camalexin and scopoletin were quantified using matrix-assisted laser desorption ionization high-resolution mass spectrometry (MALDI-HRMS). The matrix and solvent conditions were optimized to enhance sensitivity and accuracy. MS/MS experiments confirmed the identification with high mass accuracy (mass error < 5 ppm). RESULTS: The method demonstrated high linearity for scopoletin (R 2 = 0.9992) and camalexin (R 2 = 0.9987) over concentration ranges of 0.16-5 µM and 0.31-5 µM, respectively. The limits of detection (LOD) were 0.16 µM for camalexin and 0.04 µM for scopoletin, while the limits of quantification (LOQ) were 0.31 µM for camalexin and 0.16 µM for scopoletin. The average relative standard deviation was 1.43% for scopoletin and 2.46% for camalexin, with average relative errors of 3.91% and 4.11%, respectively. CONCLUSIONS: This study presents a precise, and accurate method for the quantification of key phytoalexins in Arabidopsis thaliana. The developed MALDI-HRMS approach significantly contributes to the understanding of plant defense mechanisms and offers potential applications in agricultural and biotechnological research.

Rationale: These experiments were conducted to measure the diversity of organo-U(IV) and U(III) ions created using multidimensional tandem MS and collision-induced dissociation of halogen-substituted U VIO 2-phenide complexes [UO 2(C 6H 3FX)] +, X = Cl, Br, or I. Methods: Samples of UO 2(O 2C-C 6H 3FX) 2 were prepared by digesting UO 3 with appropriate halogen-substituted carboxylic acids in deionized water. Solutions for ESI were created by diluting the digested sample in 50:50 H 2O/CH 3OH. Precursor ions for multiple-stage tandem MS were generated by electrospray ionization (ESI). Multiple-stage collision-induced dissociation (He collision gas) in a linear quadrupole ion trap mass spectrometer was used to prepare species such as [U IVFX(C≡CH)] + and U IIIF(C≡CH)] + for subsequent study of ion-molecule reactions with adventitious neutrals in the ion trap. Results: Multiple-stage CID of the [UO 2(C 6H 3FX)] +, X= Cl, Br, or I, complexes caused removal of both “yl” oxo ligands from of the UO 2 2+ moiety to create ions such as [U IVFX(C≡CH)] + and [U IIIFX] +. For [U IVFXC≡CH] + and [U IIIFC≡CH] + products, hydrolysis to generate [U IVFX(OH)] + and [U IIIF(OH)] +, with concomitant loss of HC≡CH, was observed. When X = Cl and Br, elimination of HX was competitive with loss of HC≡CH. CID of [UO 2(C 6H 3FBr)] + and [UO 2(C 6H 3FI)] + caused reductive elimination of the respective halogen radicals to generate interesting organo-U(III) species such as [U IIIF(C≡CH)] + and [U IIIC 2] +. Conclusions: The use of “preparative” tandem mass spectrometry and a suite of halogen substituted benzoic acid ligands can be used to remove both oxo ligands of UO 2 2+ and generate a group of homologous organo-U(IV) and organo-U(III) ions for studies of intrinsic reactivity.

The analysis of natural abundance isotopes in biogenic N 2O molecules can give precious information such as the nature of their precursor. However, many uncertainties exist and further validations are necessary to confirm this method as a reliable tracer of biogeochemical cycles. In particular, current methodologies (such as the isotopocule map approach) can only estimate the combined contributions of several processes at once. In this study, we aimed to develop a new methodology capable of individually discriminating the main sources of N 2O production in soil by combining natural abundance isotopes with the use of a 15N tracer ( 15N Gas Flux method). To achieve this, we conducted parallel laboratory incubations of an agricultural soil, during which we optimized the denitrification conditions through increase of moisture and amendment of nitrate; where this nitrate was either labelled or unlabeled with 15N atoms. A new linear system combined with Monte Carlo simulation enabled the determination of N 2O source partitioning, where bacterial denitrification was identified as the dominant process (87.6%), compared to fungal denitrification (9.4%), nitrification (1.5%) and nitrifier denitrification (1.6%). This new system has been compared to a recently developed stable isotope modelling tool applying Bayesian statistics (FRAME). The results agreed generally well at the exception of lower bacterial denitrification (80%) and higher nitrifier-denitrification (9%) contributions found with the FRAME model. This new approach provides a perspective for a wider application, potentially enabling the source partitioning of nitrous oxide emissions in agroecosystems.

Rationale: Erigeron breviscapus （EB）and Erigeron multiradiatus (EM) are the two species of the genus Erigeron (Asteraceae) with extremely close genetic relationships. They were used as the same “meiduoluomi” for the treatment of plague and epidemics in traditional Tibetan medicine. But in traditional Chinese medicine, only EB is used for treatment of cerebrovascular obstruction, hemiplegia due to stroke, coronary artery obstruction, chest congestion, angina pectoris. These two Erigeron species show different effects in different traditional medicines system. Therefore, analyzing the chemical compositions of two species will not only enhance comprehension of their medicinal properties, but also foster the advancement and exploration of novel applications. However, to date, there has been no comprehensive and detailed investigation comparing the constituents of EB and EM. Methods: A methodology for rapid identification of chemical profiles from two Erigeron species was devised through the integration of UHPLC-QTOF-MS/MS and multivariate statistical analysis. Additionally, a UHPLC-PDA method was established to precisely quantify of 11 components. Results: A total of 58 constituents comprising flavonoids, phenolics acids, saponin and long chain fatty acids were elucidated. Thirteen compounds were identified as potential differentiators in chemical profiles among the two Erigeron species. For quantitative assessment, 11 bioactive compounds were simultaneously quantified across 49 batches of Erigeron species samples utilizing UHPLC-PAD with wavelengths of 325 nm, 254 nm, and 266 nm. The method demonstrated excellent precision, linearity, accuracy, repeatability, stability, and recovery. Conclusions: The findings from this study will serve as a reference for quality control, functional activity exploration, and improved clinical application based on the ingredient profiles of the two species. Furthermore, this inaugural investigation into the ingredient profiles of these two species will enhance the potential and optimal utilization of both EB and EM resources.

Rationale: Flavonoid C-glycosides have a wide range of pharmacological activities. However, there are few mass spectrometric research on C,O-disaccharide flavonoid C-glycosides and di-C,O-saccharide flavonoid C-glycosides. Their fragmentation pattern and differences have not been reported, and the fragment ion library is incomplete. Therefore, it was essential to elucidate the fragmentation patterns of disaccharide flavonoid C-glycosides, which is described in this study. Methods: Four disaccharide flavonoid C-glycosides such as vitexin-4″- O-glucoside were analyzed by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometer (UPLC-MS/MS) in both positive and negative ion modes. each ion and its proposed fragmentation pathways of the four disaccharide flavonoid C-glycosides were analyzed comprehensively. Finally, Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and the established fragmentation patterns have been used to identify disaccharide flavonoid C-glycosides in Odontosoria Chinensis. Results: The fragmentation pathways of C,O-disaccharide flavonoid C-glycosides and di-C,O-saccharide flavonoid C-glycosides. are similar. they both have the mass spectrometric characteristics of O-glycoside and C-glycoside. Fragment ions after mixed pathways of neutral fragments such as saccharide ring fragment, O-glycosides, H 2O and CH 2O detraction appeared in both types of flavonoid C-glycosides, but their relative abundances are significantly different. According to the established fragmentation patterns, di-C,O-saccharide flavonoid glycosides were also found in Odontosoria Chinensis. Conclusion: The fragment ions of m/z 431, 413, 341, 311, 293, 282 in negative ion mode and m/z 293, 282, 577, 559, 541, 523, 529 and 499 in positive ion mode can serves as the main characteristics for identifying C,O-disaccharide flavonoid C-glycosides and di-C,O-saccharide flavonoid C-glycosides.

During our careers, we met Jean-François Muller essentially in the context of scientific meetings and PhD examination panels, in relation with the use of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. However, one of us (PCM) had also the opportunity to meet him in a less well-known aspect of his implication in societal activities related to the monitoring of air quality. In this recollection of Jean-François Muller, we would like to recall how his science has also served societal causes.

Aim: Cupressus torulosa (family Cupressaceae), widely distributed in the north western Himalayan region of India, is a coniferous aromatic tree with various traditional uses of its aerial parts. Its needles have been used for anti-inflammatory, anticonvulsant, antimicrobial, and wound-healing properties. Antioxidants are pivotal in mitigating oxidative stress, a contributing factor to various diseases and aging processes. Employing a diverse array of analytical techniques, ranging from TPC, TFC to in vitro, in vivo assays and UPLC-QTOF-MS the research assesses the antioxidant potential of the Cupressus torulosa. Mаteriаls аnd methods: Employing а diverse аrrаy of аnаlyticаl techniques, rаnging from TPC, TFC to in vitro, in vivo аnd ex- vivo аssаys аnd UPLC-QTOF-MS the reseаrch аssesses the аntioxidаnt potentiаl of the plаnt. The initiаl screenings reveаl promising аntioxidаnt properties of the extrаct, with vаlues of 55.28± 57.07*,52.27± 19.50 in SGOT, SGPT (IU/L) аssаys respectively when compаred to positive control glibenclаmide. With subsequent frаctionаtion into butаnol аnd ethyl аcetаte frаctions. The ethyl аcetаte frаction exhibited pаrticulаrly notаble аctivity with lower vаlue of EC50 vаlue of 85.6 μg/mL in DPPH аssаy offering insights into the mechаnisms аnd effectiveness of these compounds in scаvenging free rаdicаls аnd mitigаting oxidаtive dаmаge. Results аnd Conclusion: Moreover, the chemicаl composition of аctive frаctions undergoes chаrаcterizаtion utilizing UHPLC-QTOF-MS, fаcilitаting the identificаtion of 34 metаbolites identified in negаtive mode with 10 key аntioxidаnt compounds аnd the elucidаtion of their frаgmentаtion pаtterns. These findings underscore the potentiаl of C. torulosа аs а bountiful reservoir of bioаctive аntioxidаnts, emphаsizing their significаnce in phаrmаceuticаl аnd nutrаceuticаl аpplicаtions. This reseаrch mаkes а substаntiаl contribution towаrds identifying potent аntioxidаnt compounds, emphаsizing the need for future efforts in isolаting аnd clinicаlly testing them. It enhаnces our understаnding of nаturаl аntioxidаnts аnd their criticаl role in enhаncing heаlth аnd аddressing oxidаtive-relаted conditions.

Gas chromatography-mass spectrometry (GC-MS) is a cornerstone technique for analyses of semi-volatile compounds, constantly evolving to meet new challenges. The adoption of Time-of-flight mass spectrometers (TOF MS) has enhanced GC-MS with faster spectral acquisition and broader mass coverage, enabling rapid GC separations and even faster two-dimensional GCxGC analyses. Multi-reflecting TOF MS (MRT) further improves resolution compared to traditional TOF MS, facilitating the detection of minor analytes within complex matrices. This paper presents a significant improvement in MRT sensitivity and dynamic range achieved through a strong ion beam compression within the ion guide and the use of a conventionally oriented orthogonal accelerator. Sensitivity is improved to 100,000 ion/pg at a resolution of R=25,000, enabling the detection of low fg analyte quantities within 3 μg of matrix at 10 ng/s matrix fluxes. The demonstrated linear dynamic range exceeding 6 orders of magnitude potentially enables even deeper exploration of complex mixtures, which is crucial for ultra-trace analyses and metabolomic studies.

not-yet-known not-yet-known not-yet-known unknown An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of three ephedrine psychoactive substances in water. By optimizing chromatography conditions, mass spectrometry parameters, and solid-phase extraction (SPE) conditions (including the SPE column, sample pH, washing, and elution), the optimal treatment conditions were determined. Poly-Sery MCX was selected as the extraction column, with samples loaded at pH 3. A 4 mL solution of 2% formic acid in water was used as the eluent, and a 5 mL solution of 5% ammonia in acetonitrile was used to elute the target compounds. The best results were obtained when the residue was redissolved in acetonitrile after nitrogen evaporation. The method exhibited a good linear relationship in the range of 0-50.00 μg/L, with determination coefficients (R 2) greater than 0.9990. The detection limit and quantitation limit were 0.05-0.10 μg/L and 0.20-0.50 μg/L, respectively. Recovery rates of the target compounds in blank sewage at three different concentration levels ranged from 92.37% to 106.31%, with relative standard deviations (RSD) of 0.77-4.83% (n=7). This method has been successfully applied to the analysis of surface water and domestic sewage, demonstrating stable treatment effects and practical significance for detecting ephedrine psychoactive substances in water.