Electrospray Research Articles

Negative-Ion Electron Capture Dissociation of MALDI-Generated Peptide Anions.

Negative-ion electron capture dissociation (niECD) is an anion MS/MS technique that provides fragmentation analogous to conventional ECD, including high peptide sequence coverage and retention of labile post-translational modifications (PTMs). niECD has been proposed to be the most efficient for salt-bridged zwitterionic precursor ion structures. Several important PTMs, e.g., sulfation and phosphorylation, are acidic and can, therefore, be challenging to characterize in the positive-ion mode. Furthermore, PTM-friendly techniques, such as ECD, require multiple precursor ion-positive charges. By contrast, singly charged ions, refractory to ECD, are most compatible with niECD. Because electrospray ionization (ESI) typically yields multiply charged ions, we sought to explore matrix-assisted laser desorption/ionization (MALDI) in combination with niECD. However, the requirement for zwitterionic gaseous structures may preclude efficient niECD of MALDI-generated anions. Unexpectedly, we found that niECD of anions from MALDI is not only possible but proceeds with similar or higher efficiency compared with ESI-generated anions. Matrix selection did not appear to have a major effect. With MALDI, niECD is demonstrated up to m/z ∼4300. For such larger analytes, multiple electron captures are observed, resulting in triply charged fragments from singly charged precursor ions. Such charge-increased fragments show improved detectability. Furthermore, significantly improved (∼20-fold signal-to-noise increase) niECD spectral quality is achieved with equivalent sample amounts from MALDI vs ESI. Overall, the reported combination with MALDI significantly boosts the analytical utility of niECD.

Machine Learning-Based Integrated Multiomics Characterization of Colorectal Cancer Reveals Distinctive Metabolic Signatures.

The metabolic signature identification of colorectal cancer is critical for its early diagnosis and therapeutic approaches that will significantly block cancer progression and improve patient survival. Here, we combined an untargeted metabolic analysis strategy based on internal extractive electrospray ionization mass spectrometry and the machine learning approach to analyze metabolites in 173 pairs of cancer samples and matched normal tissue samples to build robust metabolic signature models for diagnostic purposes. Screening and independent validation of metabolic signatures from colorectal cancers via machine learning methods (Logistic Regression_L1 for feature selection and eXtreme Gradient Boosting for classification) was performed to generate a panel of seven signatures with good diagnostic performance (the accuracy of 87.74%, sensitivity of 85.82%, and specificity of 89.66%). Moreover, seven signatures were evaluated according to their ability to distinguish between cancer and normal tissues, with the metabolic molecule PC (30:0) showing good diagnostic performance. In addition, genes associated with PC (30:0) were identified by multiomics analysis (combining metabolic data with transcriptomic data analysis) and our results showed that PC (30:0) could promote the proliferation of colorectal cancer cell SW480, revealing the correlation between genetic changes and metabolic dysregulation in cancer. Overall, our results reveal potential determinants affecting metabolite dysregulation, paving the way for a mechanistic understanding of altered tissue metabolites in colorectal cancer and design interventions for manipulating the levels of circulating metabolites.

Coupling Miniaturized Stir Bar Sorptive Dispersive Microextraction to Needle-Based Electrospray Ionization Emitters for Mass Spectrometry: Determination of Tetrahydrocannabinol in Human Saliva as a Proof of Concept.

Direct coupling of sample preparation with mass spectrometry (MS) can speed up analysis, enabling faster decision-making. In such combinations, where the analysis time is mainly defined by the extraction procedure, magnetic dispersive solid-phase extraction emerges as a relevant technique because of its rapid workflow. The dispersion and retrieval of the magnetic sorbent are typically uncoupled stages, thus reducing the potential simplicity. Stir bar sorptive dispersive microextraction (SBSDME) is a novel technique that integrates both stages into a single device. Its miniaturization (mSBSDME) makes it more portable and compatible with low-availability samples. This article reports the direct combination of mSBSDME and MS using a needle-based electrospray ionization (NESI) emitter as the interface. This combination is applied to determine tetrahydrocannabinol in saliva samples, a relevant societal problem if the global consumption rates of cannabis are considered. The coupling requires only the transference of the magnet (containing the sorbent and the isolated analyte) from the mSBSDME to the hub of a hypodermic needle, where the online elution occurs. The application of 5 kV on the needle forms an electrospray on its tip, transferring the ionized analyte to the MS inlet. The excellent performance of mSBSDME-NESI-MS/MS relies on the sensitivity (limits of detection as low as 2.25 ng mL-1), the precision (relative standard deviation lower than 15%), and the accuracy (relative recoveries ranged from 87 to 127%) obtained. According to the results, the mSBSDME-NESI-MS/MS technique promises faster and more efficient chemical analysis in MS-based applications.

Development of shake powdered food with cocoa, mesquite pod flour, oak extract and agave fructans, quality characteristics and glycemic index

Purpose The purpose of this study was to development of a new chocolate-flavored powdered food supplement enriched with mesquite pod flour, oak extract and agave fructans, with proper sensory characteristics as well as its physicochemical and glycemic quality. Design/methodology/approach A powdered shake was formulated using experimental design (23) with mesquite (Prosopis laevigata) pod flour, oak (Quercus convallata) extracts, nonalkalinized cocoa, agave fructans, milk protein and xanthan gum. Sensory analysis (choice profile method, ranking test, focus group, quantitative descriptive analysis), moisture, ash, fiber, protein and lipids, pH, color, wettability, dispersibility and rheological tests were done. Phenolic profiling analysis to samples was done by ultraperformance liquid chromatography coupled to photodiode array detection and electrospray ionization tandem mass spectrometry, antioxidant activity was measured by 2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation, ferric reducing antioxidant power and oxygen radical absorbance capacity, glycemic index (GI) and glycemic load were evaluated. Findings The main sensory attributes in the powders were chocolate, bitter, astringent, grass/linseed flavors (p < 0.05). The product has protein [66.9%], carbohydrates [22.0%], lipids [1.6%], ash [2.7%] and moisture [6.8%], with wettability (23 s), and dispersibility of 77.9%. Catechin, epicatechin, gallocatechin, procyanidin B2, chlorogenic, coumaric and ferulic acids were identified. GI and caloric load not show differences between men (73.3±2.4, 4.4±0.1) and women (67.0±2.1, 4.1±0.1) (p > 0.05). Originality/value The use of mesquite pods, oak and agave fructans in powder food supplement is an alternative to obtain a product high in protein, with good sensory properties, antioxidant activity and moderate GI.

Top-down mass spectrometry of native proteoforms and their complexes: a community study.

The combination of native electrospray ionization with top-down fragmentation in mass spectrometry (MS) allows simultaneous determination of the stoichiometry of noncovalent complexes and identification of their component proteoforms and cofactors. Although this approach is powerful, both native MS and top-down MS are not yet well standardized, and only a limited number of laboratories regularly carry out this type of research. To address this challenge, the Consortium for Top-Down Proteomics initiated a study to develop and test protocols for native MS combined with top-down fragmentation of proteins and protein complexes across 11 instruments in nine laboratories. Here we report the summary of the outcomes to provide robust benchmarks and a valuable entry point for the scientific community.

Data Acquisition and Intraoperative Tissue Analysis on a Mobile, Battery-Operated, Orbitrap Mass Spectrometer.

Mass spectrometry has been increasingly explored in intraoperative studies as a potential technology to help guide surgical decision making. Yet, intraoperative experiments using high-performance mass spectrometry instrumentation present a unique set of operational challenges. For example, standard operating rooms are often not equipped with the electrical requirements to power a commercial mass spectrometer and are not designed to accommodate their permanent installation. These obstacles can impact progress and patient enrollment in intraoperative clinical studies because implementation of MS instrumentation becomes limited to specific operating rooms that have the required electrical connections and space. To expand our intraoperative clinical studies using the MasSpec Pen technology, we explored the feasibility of transporting and acquiring data on Orbitrap mass spectrometers operating on battery power in hospital buildings. We evaluated the effect of instrument movement including acceleration and rotational speeds on signal stability and mass accuracy by acquiring data using direct infusion electrospray ionization. Data were acquired while rolling the systems in/out of operating rooms and while descending/ascending a freight elevator. Despite these movements and operating the instrument on battery power, the relative standard deviation of the total ion current was <5% and the magnitude of the mass error relative to the internal calibrant never exceeded 5.06 ppm. We further evaluated the feasibility of performing intraoperative MasSpec Pen analysis while operating the Orbitrap mass spectrometer on battery power during an ovarian cancer surgery. We observed that the rich and tissue-specific molecular profile commonly detected from ovarian tissues was conserved when running on battery power. Together, these results demonstrate that Orbitrap mass spectrometers can be operated and acquire data on battery power while in motion and in rotation without losses in signal stability or mass accuracy. Furthermore, Orbitrap mass spectrometers can be used in conjunction to the MasSpec Pen while on battery power for intraoperative tissue analysis.

Probing the Architecture of Multisubunit Protein Complexes with In-line Disulfide Reduction and Native MS Analysis.

Native mass spectrometry (MS) continues to enjoy growing popularity as a means of providing a wealth of information on noncovalent biopolymer assemblies ranging from composition and binding stoichiometry to characterization of the topology of these assemblies. The latter frequently relies on supplementing MS measurements with limited fragmentation of the noncovalent complexes in the gas phase to identify the pairs of neighboring subunits. While this approach has met with much success in the past two decades, its implementation remains difficult (and the success record relatively modest) within one class of noncovalent assemblies: protein complexes in which at least one binding partner has multiple subunits cross-linked by disulfide bonds. We approach this problem by inducing chemical reduction of disulfide bonds under nondenaturing conditions in solution followed by native MS analysis with online buffer exchange to remove unconsumed reagents that are incompatible with the electrospray ionization process. While this approach works well with systems comprised of thiol-linked subunits that remain stable upon reduction of the disulfide bridges (such as immunoglobulins), chemical reduction frequently gives rise to species that are unstable (prone to aggregation). This problem is circumvented by taking advantage of the recently introduced cross-path reactive chromatography platform (XPRC), which allows the disulfide reduction to be carried out in-line, thereby minimizing the loss of metastable protein subunits and their noncovalent complexes with the binding partners prior to MS analysis. The feasibility of this approach is demonstrated using hemoglobin complexes with haptoglobin 1-1, a glycoprotein consisting of four polypeptide chains cross-linked by disulfide bonds.

Machine Learning Models Identify Inhibitors of New Delhi Metallo-β-lactamase.

The worldwide spread of the metallo-β-lactamases (MBL), especially New Delhi metallo-β-lactamase-1 (NDM-1), is threatening the efficacy of β-lactams, which are the most potent and prescribed class of antibiotics in the clinic. Currently, FDA-approved MBL inhibitors are lacking in the clinic even though many strategies have been used in inhibitor development, including quantitative high-throughput screening (qHTS), fragment-based drug discovery (FBDD), and molecular docking. Herein, a machine learning-based prediction tool is described, which was generated using results from HTS of a large chemical library and previously published inhibition data. The prediction tool was then used for virtual screening of the NIH Genesis library, which was subsequently screened using qHTS. A novel MBL inhibitor was identified and shown to lower minimum inhibitory concentrations (MICs) of Meropenem for a panel of E. coli and K. pneumoniae clinical isolates expressing NDM-1. The mechanism of inhibition of this novel scaffold was probed utilizing equilibrium dialyses with metal analyses, native state electrospray ionization mass spectrometry, UV-vis spectrophotometry, and molecular docking. The uncovered inhibitor, compound 72922413, was shown to be 9-hydroxy-3-[(5-hydroxy-1-oxa-9-azaspiro[5.5]undec-9-yl)carbonyl]-4H-pyrido[1,2-a]pyrimidin-4-one.

A validated high‐performance liquid chromatography‐tandem mass spectrometry method for simultaneous determination of irinotecan and two major metabolites in rat plasma: Application for the pharmacokinetics study

AbstractA high‐performance liquid chromatography‐tandem mass spectrometry method has been developed for the determination of irinotecan, 7‐ethyl‐10‐hydroxycamptothecin (SN38), and SN38 glucuronide (SN38G) in rat plasma in the present study. The analytes were separated on a C18 column and a triple‐quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. Irinotecan, SN38 and SN38G could be well retained in the C18 column after optimization of mobile phase. A simple protein precipitation was used to pretreat the plasma. The extraction recovery was above 90% and the matrix effect could be negligible. The method was linear over the concentration ranges of 3.46–3458.8 ng/mL for irinotecan, 2.53–2530.0 ng/mL for SN38 and 2.5–2500.0 ng/mL for SN38G. The precision and accuracy was within the acceptable limits. The simple and convenient method was validated and successfully applied to support the pharmacokinetic study and elucidate the mechanism of irinotecan‐induced diarrhea after irinotecan was intravenously injected to the Sprague‐Dawley rats.

Development and validation of a UHPLC-ESI-MS/MS method for the simultaneous determination of organic acids and phenolic compounds in Filipendula vulgaris, Polygonum divaricatum, Hypericum linarioides, and Rheum ribes

This research focused on investigating biologically active and pharmaceutically important phytochemicals using reliable and reproducible analytical techniques specifically designed for traditional medicinal plants. Considering the complex chemical diversity present in plant extracts, reliable identification methods are crucial. The goal of this study was to develop and validate a robust UHPLC-ESI-MS/MS method for the qualitative and quantitative analysis of organic acids (OAs) and phenolic compounds (PCs). With gradient elution of water containing 0.1 % formic acid and acetonitrile containing 0.1 % formic acid as the mobile phase, OAs and PCs were separated chromatographically on a C18 reversed-phase column. Through the use of an electrospray ionization source operating in negative ionization mode, these compounds were identified on a triple quadrupole tandem mass spectrometer. The validation results clearly indicate that the method exhibited linearity with a squared correlation coefficient (R2 ≥ 0.9986), demonstrating sensitivity (LOQ: 1.08 µg/L-10.79 µg/L), precision (RSD%≤2.73), and trueness (RE% ≤ 1.53) for the OAs and PCs found in the plants. The developed UHPLC-ESI-MS/MS method was successfully applied to the qualitative and quantitative analysis of OAs and PCs in Turkish plants, which are commonly used in traditional medicine. Our study identified a total of 12 OAs and PCs in F. vulgaris, 12 in P. divaricatum, 9 in H. linarioides, and 11 in R. ribes. In particular, gallic acid had the highest content in F. vulgaris (925.67 µg/g extract) and R. ribes (1358.78 µg/g extract), while H. linarioides (730.66 µg/g extract) and P. divaricatum (4003.02 µg/g extract) had relatively high levels of quinic acid. In conclusion, the developed UHPLC-ESI-MS/MS method allows the simultaneous analysis and quantification of 2 OAs and 33 PCs in plants and proves to be a valuable tool for evaluating the efficacy of traditional medicinal plants.

Codetermination of antimicrobial agents in rabbit tear fluid using LC-MS/MS assay: Insights into ocular pharmacokinetic study.

Managing ocular microbial infections typically requires pharmacotherapy using antibiotic eye drops, such as moxifloxacin hydrochloride (MFX), combined with an antifungal agent like amphotericin B (AB). We carried out and validated an LC-MS/MS assay to quantify these compounds in rabbit tear fluid in order to look into the pharmacokinetics of these two drugs. We employed a protein precipitation technique for the extraction of drugs under examination. A Waters Symmetry C18 column was used to separate the analytes and internal standard. The composition of the mobile phase was like (A) 0.1% v/v formic acid in water and (B) methanol. The detection of MFX and AB was accomplished through the utilization of positive ion electrospray ionization under multiple reaction monitoring mode. The linearity curves for both analytes exhibited an acceptable trendline across a concentration range of 2.34-300 ng/mL for MFX and 7.81-1000 ng/mL for AB in surrogate rabbit tear fluid. The lower limit of quantitation for MFX was 2.34 ng/mL, while for AB, it was 7.81 ng/mL. The approach was strictly validated, encompassing tests of selectivity, linearity (with r2>0.99), precision, accuracy, matrix effects, and stability. Consequently, we employed this method to evaluate the pharmacokinetics profiles of MFX and AB in rabbit tear fluid following single topical doses.

Top-Down Proteomics Analysis of Picogram-Level Complex Samples Using Spray-Capillary-Based Capillary Electrophoresis-Mass Spectrometry.

Proteomics analysis of mass-limited samples has become increasingly important for understanding biological systems in physiologically relevant contexts such as patient samples, multicellular organoids, spheroids, and single cells. However, relatively low sensitivity in top-down proteomics methods makes their application to mass-limited samples challenging. Capillary electrophoresis (CE) has emerged as an ideal separation method for mass-limited samples due to its high separation resolution, ultralow detection limit, and minimal sample volume requirements. Recently, we developed "spray-capillary", an electrospray ionization (ESI)-assisted device, that is capable of quantitative ultralow-volume sampling (e.g., pL-nL level). Here, we developed a spray-capillary-CE-MS platform for ultrasensitive top-down proteomics analysis of intact proteins in mass-limited complex biological samples. Specifically, to improve the sensitivity of the spray-capillary platform, we incorporated a polyethylenimine (PEI)-coated capillary and optimized the spray-capillary inner diameter. Under optimized conditions, we successfully detected over 200 proteoforms from 50 pg of E. coli lysate. To our knowledge, the spray-capillary CE-MS platform developed here represents one of the most sensitive detection methods for top-down proteomics. Furthermore, in a proof-of-principle experiment, we detected 261 ± 65 and 174 ± 45 intact proteoforms from fewer than 50 HeLa and OVCAR-8 cells, respectively, by coupling nanodroplet-based sample preparation with our optimized CE-MS platform. Overall, our results demonstrate the capability of the modified spray-capillary CE-MS platform to perform top-down proteomics analysis on picogram amounts of samples. This advancement presents the possibility of meaningful top-down proteomics analysis of mass-limited samples down to the level of single mammalian cells.

Investigation of half-sandwich platinum group metal complexes featuring benzamide derived ligands and their diazido derivatives: Synthesis, molecular structures and biological studies

Benzamide derivative ligands L1 and L2 were synthesized and reactions of these ligands with metal dimers [Ru(p-cymene)Cl2]2 and [Cp*MCl2]2 (M = Rh/Ir) yielded a series of “piano-stool”-type neutral mononuclear metal-arene-benzamide complexes (1, 2, 3, 4, 5 and 6) of the general formula [(arene)M(κ1(N)L)Cl2] (where arene = p-cymene and Cp*, M = Ru, Rh and Ir and L = L1 and L2). Further treatment of the neutral complexes 1-6 with sodium azide in methanol resulted in the formation of diazido complexes 7, 8, 9 and 10. Crystallographic studies of the complexes 2, 5, 7 and 8 revealed the ligands coordinated to the metal centers through the nitrogen atom of thiazole/thiadiazole ring in a monodentate fashion. The complexes were characterized by NMR, FTIR, UV-Vis spectroscopy and ESI-mass spectrometry. All the ligands and metal complexes were screened for their antibacterial and antioxidant activities. Interestingly, it was observed that only the diazido complexes were active towards the Gram-positive Staphylococcus aureus bacterial strains, with activities more than the standard. Antioxidant study revealed that the compounds possess insignificant activities.

Simultaneous Quantification of Vancomycin, Linezolid and Voriconazole in Human Plasma by UHPLC–MS/MS: Application in Therapeutic Drug Monitoring

Abstract Objective Individual differences challenge the treatment of vancomycin, linezolid and voriconazole in severe infections. This study aimed to build a simple and economical method for simultaneous determination of the three antibiotics in human plasma by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) and provided a reference for therapeutic drug monitoring (TDM) of infected patients. Methods The plasma samples were precipitated by acetonitrile and detected and separated on a shim-pack GIST C18 column following the gradient elution within 5 min. Mass quantification was performed on multiple reaction monitoring mode under positive electrospray ionization. Results The linear ranges of vancomycin, linezolid and voriconazole were 1.00–100.00, 0.10–15.00 and 0.10–20.00 μg·mL−1, respectively, with good linearity (R2 &amp;gt; 0.99). The accuracy and precision, matrix effect, extraction recovery and stability were validated, and the results all meet the acceptance criteria of China Food and Drug Administration (CFDA) guidelines. Conclusion The UHPLC–MS/MS method was established and validated for the simultaneous determination of vancomycin, linezolid and voriconazole in human plasma and successfully applied to routine TDM for individualized treatment.

Diaporchalasins A-E, New Cytochalasins from the Endophytic Fungus Diaporthe sp. BMX12 Isolated from Aquilaria sinensis.

Five new cytochalasins, diaporchalasins A-E (1-5), together with 14 known congeners (6-19) were isolated from the endophytic fungus Diaporthe sp. BMX12, which was isolated from the branches of Aquilaria sinensis. The structures of the new compounds were elucidated by extensive spectroscopic analyses including high-resolution electron spray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR). Their absolute configurations were assigned by theoretical electronic circular dichroism (ECD) calculations. Compounds 11 and 12 featuring a keto carbonyl at C-21 displayed cytotoxicity toward K562, BEL-7402, SGC-7901, A549, and HeLa cell lines with IC50 values ranging from 4.4 to 47.4 μM.

Real-Time Identification of Aerosol-Phase Carboxylic Acid Production Using Extractive Electrospray Ionization Mass Spectrometry.

Comprehensive identification of aerosol sources and their constituent organic compounds requires aerosol-phase molecular-level characterization with a high time resolution. While real-time chemical characterization of aerosols is becoming increasingly common, information about functionalization and structure is typically obtained from offline methods. This study presents a method for determining the presence of carboxylic acid functional groups in real time using extractive electrospray ionization mass spectrometry based on measurements of [M - H + 2Na]+ adducts. The method is validated and characterized using standard compounds. A proof-of-concept application to α-pinene secondary organic aerosol (SOA) shows the ability to identify carboxylic acids even in complex mixtures. The real-time capability of the method allows for the observation of the production of carboxylic acids, likely formed in the particle phase on short time scales (<120 min). Our research explains previous findings of carboxylic acids being a significant component of SOA and a quick decrease in peroxide functionalization following SOA formation. We show that the formation of these acids is commensurate with the increase of dimers in the particle phase. Our results imply that SOA is in constant evolution through condensed-phase processes, which lower the volatility of the aerosol components and increase the available condensed mass for SOA growth and, therefore, aerosol mass loading in the atmosphere. Further work could aim to quantify the effect of particle-phase acid formation on the aerosol volatility distributions.

Paper-in-Tip Bipolar Electrospray Mass Spectrometry for Real-Time Chemical Reaction Monitoring.

Capturing short-lived intermediates at the molecular level is key to understanding the mechanism and dynamics of chemical reactions. Here, we have developed a paper-in-tip bipolar electrolytic electrospray mass spectrometry platform, in which a piece of triangular conductive paper incorporated into a plastic pipette tip serves not only as an electrospray emitter but also as a bipolar electrode (BPE), thus triggering both electrospray and electrolysis simultaneously upon application of a high voltage. The bipolar electrolysis induces a pair of redox reactions on both sides of BPE, enabling both electro-oxidation and electro-reduction processes regardless of the positive or negative ion mode, thus facilitating access to complementary structural information for mechanism elucidation. Our method enables real-time monitoring of transient intermediates (such as N,N-dimethylaniline radical cation, dopamine o-quinone (DAQ) and sulfenic acid with half-lives ranging from microseconds to minutes) and transient processes (such as DAQ cyclization with a rate constant of 0.15 s-1). This platform also provides key insights into electrocatalytic reactions such as Fe (III)-catalyzed dopamine oxidation to quinone species at physiological pH for neuromelanin formation.

Paper‐in‐Tip Bipolar Electrospray Mass Spectrometry for Real‐Time Chemical Reaction Monitoring

Capturing short‐lived intermediates at the molecular level is key to understanding the mechanism and dynamics of chemical reactions. Here, we have developed a paper‐in‐tip bipolar electrolytic electrospray mass spectrometry platform, in which a piece of triangular conductive paper incorporated into a plastic pipette tip serves not only as an electrospray emitter but also as a bipolar electrode (BPE), thus triggering both electrospray and electrolysis simultaneously upon application of a high voltage. The bipolar electrolysis induces a pair of redox reactions on both sides of BPE, enabling both electro‐oxidation and electro‐reduction processes regardless of the positive or negative ion mode, thus facilitating access to complementary structural information for mechanism elucidation. Our method enables real‐time monitoring of transient intermediates (such as N,N‐dimethylaniline radical cation, dopamine o‐quinone (DAQ) and sulfenic acid with half‐lives ranging from microseconds to minutes) and transient processes (such as DAQ cyclization with a rate constant of 0.15 s−1). This platform also provides key insights into electrocatalytic reactions such as Fe (III)‐catalyzed dopamine oxidation to quinone species at physiological pH for neuromelanin formation.

Exhaled breath analysis in patients with potentially curative lung cancer undergoing surgery: a longitudinal study.

Exhaled breath analysis has emerged as a non-invasive and promising method for early detection of lung cancer, offering a novel approach for diagnosis through the identification of specific biomarkers present in a patient's breath. For this longitudinal study, 29 treatment-naive patients with lung cancer were evaluated before and after surgery. Secondary electrospray ionization high-resolution mass spectrometry was used for exhaled breath analysis. Volatile organic compounds with absolute log2 fold change ≥ 1 and q-values ≥ 0.71 were selected as potentially relevant. Exhaled breath analysis resulted in a total of 3482 features. 515 features showed a substantial difference before and after surgery. The small sample size generated a false positive rate of 0.71, therefore, around 154 of these 515 features were expected to be true changes. Biological identification of the features with the highest consistency (m/z -242.18428 and m/z -117.0539) revealed to potentially be 3-Oxotetradecanoic acid and Indole, respectively. Principal component analysis revealed a primary cluster of patients with a recurrent lung cancer, which remained undetected in the initial diagnostic and surgical procedures. The change of exhaled breath patterns after surgery in lung cancer emphasizes the potential for lung cancer screening and detection.

Determination of Sulfites in Dried Fruits by Paper Spray Ionization Tandem Mass Spectrometry

Sulfite, a widely used food additive, is subject to regulated labeling. The extraction of sulfite as the stable hydroxymethylsulfonate (HMS) form and its quantitative analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been recognized for their good sensitivity, selectivity, and versatility across various food materials. This study aimed to develop a cost-effective and simpler method for sulfite quantitation, while maintaining the superior sensitivity and selectivity of mass spectrometry (MS). To achieve this, we introduced paper spray ionization (PSI), an ambient desorption ionization technique that could achieve the direct measurement of analytes without employing separation. We also employed a novel internal standard (IS) structurally similar to the analyte, replacing the more expensive isotopically labeled IS. Although the PSI-MS/MS method developed in this study exhibited slightly lower analytical performance compared to the conventional LC-MS/MS, it remained effective for sulfite analysis in dried fruits.