Low-resolution Mass Spectrometry Research Articles

Photophysics of Isolated Rose Bengal Anions

Dye molecules based on the xanthene moiety are widely used as fluorescent probes in bioimaging and technological applications due to their large absorption cross-section for visible light and high fluorescence quantum yield. These applications require a clear understanding of the dye's inherent photophysics and the effect of a condensed-phase environment. Here, the gas-phase photophysics of the rose bengal doubly deprotonated dianion [RB - 2H]2-, deprotonated monoanion [RB - H]-, and doubly deprotonated radical anion [RB - 2H]•- is investigated using photodetachment, photoelectron, and dispersed fluorescence action spectroscopies, and tandem ion mobility spectrometry (IMS) coupled with laser excitation. For [RB - 2H]2-, photodetachment action spectroscopy reveals a clear band in the visible (450-580 nm) with vibronic structure. Electron affinity and repulsive Coulomb barrier (RCB) properties of the dianion are characterized using frequency-resolved photoelectron spectroscopy, revealing a decreased RCB compared with that of fluorescein dianions due to electron delocalization over halogen atoms. Monoanions [RB - H]- and [RB - 2H]•- differ in nominal mass by 1 Da but are difficult to study individually using action spectroscopies that isolate target ions using low-resolution mass spectrometry. This work shows that the two monoanions are readily distinguished and probed using the IMS-photo-IMS and photo-IMS-photo-IMS strategies, providing distinct but overlapping photodissociation action spectra in the visible spectral range. Gas-phase fluorescence was not detected from photoexcited [RB - 2H]2- due to rapid electron ejection. However, both [RB - H]- and [RB - 2H]•- show a weak fluorescence signal. The [RB - H]- action spectra show a large Stokes shift of ∼1700 cm-1, while the [RB - 2H]•- action spectra show no appreciable Stokes shift. This difference is explained by considering geometries of the ground and fluorescing states.

Deep Learning Driven GC-MS Library Search and Its Application for Metabolomics

Preliminary compound identification and peak annotation in gas chromatography-mass spectrometry is usually made using mass spectral databases. There are a few algorithms that enable performing a search of a spectrum in a large mass spectral library. In many cases, a library search procedure returns a wrong answer even if a correct compound is contained in a library. In this work, we present a deep learning driven approach to a library search in order to reduce the probability of such cases. Machine learning ranking (learning to rank) is a class of machine learning and deep learning algorithms that perform a comparison (ranking) of objects. This work introduces the usage of deep learning ranking for small molecules identification using low-resolution electron ionization mass spectrometry. Instead of simple similarity measures for two spectra, such as the dot product or the Euclidean distance between vectors that represent spectra, a deep convolutional neural network is used. The deep learning ranking model outperforms other approaches and enables reducing a fraction of wrong answers (at rank-1) by 9-23% depending on the used data set. Spectra from the Golm Metabolome Database, Human Metabolome Database, and FiehnLib were used for testing the model.

Mass spectrometry characterization of anticoagulant rodenticides and hydroxyl metabolites.

Anticoagulant rodenticides (ARs) are used worldwide for rodent population control to protect human health and biodiversity, and to prevent agricultural and economic losses. Rodents may develop a metabolic resistance to ARs. In order to help understand such metabolic resistance, mass spectrometry was used to position the hydroxylated group of hydroxyl metabolites of second-generation ARs (SGARs). Most AR pesticides are derived from the 4-hydroxycoumarin/thiocoumarin family. We used low-resolution and high-resolution mass spectrometry to understand the fragmentation pathways of the ARs and their respective metabolites, and to better define the structure of their tandem mass spectrometry product ions. Seven specific product ions were evidenced for five ARs, with their respective chemical structures. Those ions were obtained as well from the mass spectra of the hydroxyl metabolites of four SGARs, difenacoum (DFM), brodifacoum (BFM), difethialone (DFTL) and flocoumafen (FLO), with different positions of the hydroxyl group. The differences in chemical structure between DFM on the one hand and BFM, FLO and DFTL on the other could explain the differences in bioavailability between these two groups of molecules. The defined product ions will be used to investigate the part played by the metabolic issue in the field resistance of SGARs.

UPLC-MS-Based Procedures to Detect Prolyl-Hydroxylase Inhibitors of HIF in Urine.

This article presents newly developed screening and confirmation analytical procedures to detect the misuse of nine prolyl-hydroxylase inhibitors of the hypoxia-inducible factor: daprodustat, desidustat, FG2216, IOX2, IOX4, JNJ-42041935, molidustat, roxadustat and vadadustat, targeting either the parent drugs and/or their main metabolite(s). For the sample pretreatment, different extraction protocols and technologies were evaluated. The instrumental analysis was performed by ultra-high-performance liquid chromatography coupled to either high- or low-resolution mass spectrometry. The chromatographic separation was performed on a C18 column, employing water and acetonitrile, both containing 0.1% formic acid, as mobile phase. Detection was achieved using as analyzer either a triple quadrupole or an Orbitrap, with positive and negative electrospray ionization and different acquisition modes. Validation of the procedures was performed according to the ISO 17025 and World Anti-Doping Agency guidelines. The methods do not show any significant interference at the retention times of the analytes of interest. The extraction efficiency was estimated to be greater than 75% for all analytes and the matrix effect smaller than 35%. Detection capability was determined in the range of 0.25-2.0 for the screening procedure and in the range of 0.5-2.0ng/mL for the confirmation procedure, that is, in a range of concentration small enough to reveal the abuse of the compounds considered, in case they are used as performance-enhancing agents. The repeatability of the relative retention times (CV%<0.5) and of the relative abundances of the selected ion transitions, considered only in the case of triple quadrupole (CV%<15), was confirmed to be fit for purpose to ensure the unambiguous identification of all the target analytes in human urine. The applicability of the newly developed methods was verified by the analysis of urine samples containing molidustat, roxadustat or daprodustat. The developed procedures enabled to detect the compounds under investigation and their main metabolites.

Does the ion mobility resolving power as provided by commercially available ion mobility quadrupole time-of-flight mass spectrometry instruments permit the unambiguous identification of small molecules in complex matrices?

Quadrupole based mass spectrometry based detection has experienced enormous improvements in terms of sensitivity over the last centuries. This development has not been equally matched with improvements in selectivity. Hence, the use of unit mass based MS/MS transitions or high resolution (HRMS) based extracted ion chromatograms is gradually becoming insufficient in the field of high sensitivity multi-residue analysis (e.g. pesticides in food). As a consequence, commercial instruments hyphenating ion mobility (IMS) with low or high resolution mass spectrometry based detection have appeared. The use of such an additional (frequently claimed to be orthogonal) dimension is intended to increase selectivity. In addition, IMS derived collision cross section (CCS) has been proposed to be used as an additional identification point for the unambiguous identification of trace compounds in complex matrices.It is the topic of this paper to investigate the benefit of using such a hyphenated technique for trace analysis of small molecules in complex matrices. The potential of CCS to serve as additional identification point has been critically evaluated. Discussed are the effect of CCS data on false detects and missing detects of analytes present at trace levels. This involves the investigation of the physical resolving power provided by HRMS, IMS and chromatography as well as the correlation among these parameters (orthogonality).It is the conclusion that currently commercially available travelling wave and linear drift tube based IMS devices with a resolving power of up to 50 permit a reduction of false detects, yet this comes at the price of a higher likelihood of missing detects. The reduction of missing detects and the use of CCS as potential confirmatory information would require IMS resolving powers above 100.

Transfer Hydrogenation of Ketones Catalyzed by Symmetric Imino-N-heterocyclic Carbene Co(III) Complexes.

The synthesis of new moisture-sensitive imine-functionalized N-heterocyclic carbene (NHC) precursor salts [1-(2-[(hydroxyl-benzylidene)-amino]-ethyl)-3-R-3H-imidazole-1-ium bromide; R = methyl (1a), ethyl (1b), and benzyl (1c)] is reported. Subsequent deprotonation of 1a–c and coordination of the in situ generated NHC ligands to CoBr2 led to the isolation of air-stable six-coordinate Co(III) complexes 2a–c, respectively. All the salts and complexes were fully characterized. Single-crystal X-ray analysis of 2a and 2c showed octahedral Co centers hexacoordinated to two NHC carbons, two imine nitrogen atoms, and two phenolate oxygens in the form [C^N^O(Co3+)C^N^O]. The complexes were used in the catalytic transfer hydrogenation (CTH) of a range of ketones in 2-propanol as the solvent and hydrogen donor. Based on a low catalyst concentration of 0.4 mol %, significant conversions in the range of 70–99% were recorded at high turnover frequencies up to 1635 h–1. A mechanism to account for the steps involved in the CTH of cyclohexanone by complex 2a is proposed and supported by data from cyclic voltammetry, low-resolution mass spectrometry, UV, and IR spectroscopic techniques.

Automated open-access liquid chromatography high resolution mass spectrometry to support drug discovery projects

The need of a continuous productivity increases in medicinal chemistry laboratories of the pharmaceutical industry motivated the development, over the years, of new software solutions to enable Open-Access in many analytical techniques such as NMR or LC, among others, to characterize and assess the purity of new molecules. These approaches have been widely spread in LC with low resolution MS systems, but similar automated platforms have been rather less explored with high resolution MS. In this work, an improved Automated Open-Access methodology on an UHPLC with DAD coupled to ESI and quadrupole time-of-flight MS system is described. Detailed reports from standard UHPLC-MS runs containing chromatograms and different spectra (MS with different fragmentation) are automatically sent to the chemists. High resolution MS data is typically achieved within ± 1 mDa mass accuracy regardless of sample concentration. Upon training, chemists log-in samples into the system by selecting appropriate methods, being able to interpret the results by themselves in 95% of the cases. The instrument is working unattended, except for a limited number of samples (5%) which require more complex experiments. To the best of our knowledge, this is the first time a completely automated Open-Access LC-HRMS approach has been implemented for medicinal chemists of a pharmaceutical industry.

Quantitative Assessment of Anti-Cancer Drug Efficacy From Coregistered Mass Spectrometry and Fluorescence Microscopy Images of Multicellular Tumor Spheroids.

Spheroids-three-dimensional aggregates of cells grown from a cancer cell line-represent a model of living tissue for chemotherapy investigation. Distribution of chemotherapeutics in spheroid sections was determined using the matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). Proliferating or apoptotic cells were immunohistochemically labeled and visualized by laser scanning confocal fluorescence microscopy (LSCM). Drug efficacy was evaluated by comparing coregistered MALDI MSI and LSCM data of drug-treated spheroids with LSCM only data of untreated control spheroids. We developed a fiducial-based workflow for coregistration of low-resolution MALDI MS with high-resolution LSCM images. To allow comparison of drug and cell distribution between the drug-treated and untreated spheroids of different shapes or diameters, we introduced a common diffusion-related coordinate, the distance from the spheroid boundary. In a procedure referred to as "peeling", we correlated average drug distribution at a certain distance with the average reduction in the affected cells between the untreated and the treated spheroids. This novel approach makes it possible to differentiate between peripheral cells that died due to therapy and the innermost cells which died naturally. Two novel algorithms-for MALDI MS image denoising and for weighting of MALDI MSI and LSCM data by the presence of cell nuclei-are also presented.

Physical and Chemical Properties of Dimedone “Base Schiff” for Organic Semiconductor Applications

One pot synthesis of “Schiff” base is carried out in this study. The synthesis by using microwave reaction as a modern method is realized from 4-dimehtylamino-5,5-dimethyl-1,3-cyclohexanedione, benzene 1.4-diamine and 1,3-benzodioxole-5-carbaldehyde. The structural properties of the resulting compound were determined by NMR (1H and 13C), low-resolution mass spectrometry (ESI–MS), FTIR spectroscopy and x-ray diffraction. The product is semicrystalline material with a monoclinic unit cell. Based on the optical spectra, the compound has an optical band gap of (Eg = 2.89 eV). In addition, the dielectric spectroscopy was applied for studying the ac-electrical conductivity, dielectric constant and dielectric losses of the synthesized “Schiff” base. The results obtained from this study show that it has a promising future in the field of organic optoelectronics and their potential applications especially in photovoltaic conversion energies.

Transfer of a Multiclass Method for over 60 Antibiotics in Food from High Resolution to Low Resolution Mass Spectrometry.

A multiclass method has been developed to screen and confirm a wide range of anti-microbial residues in muscle and milk, and validated using liquid-chromatography coupled to (low-resolution, LR) tandem mass spectrometry (LC-QqQ). Over sixty antibiotics, belonging to ten distinct families, were included in the method scope. The development process was rapidly concluded as a result of two previously implemented methods. This consisted of identical sample treatments, followed by liquid chromatography, and coupled with high-resolution (HR) mass spectrometry (LC-Q-Orbitrap). The validation study was performed in the range between 10–1500 μg·kg−1 for muscles and 2–333 μg·kg−1 for milk. The main performance characteristics were estimated and, then, compared to those previously obtained with HR technique. The validity of the method transfer was ascertained also through inter-laboratory studies.

Airborne and Dermal Exposure to Polycyclic Aromatic Hydrocarbons, Volatile Organic Compounds, and Particles among Firefighters and Police Investigators.

The main aim of this study was to assess dermal exposure to polycyclic aromatic hydrocarbons (PAHs) and airway exposure to PAHs, volatile organic compounds (VOCs; benzene and 1,3-butadiene), and particles among firefighters (FFs) and police forensic investigators (PFIs) in Sweden. Active (pump with a filter and sorbent tube) and passive (polyurethane foam -cyl and perkin elmer carbopack-tube) personal air sampling and dermal tape stripping (wrist and collar bone) were performed on seven FF team leaders during training fires and nine PFIs investigating the aftermath of live fire events. In addition, passive personal air sampling was performed on eight FF team leaders during live emergency fires. PAHs and VOCs were analysed using high-resolution gas chromatography low-resolution mass spectrometry. The mass concentration of total dust (particles) was determined using standard gravimetric methods. The air samples showed that the exposure to PAHs, benzene, 1,3-butadiene, and particles was below Swedish occupational exposure limits (OELs). Naphthalene was the predominant PAH in all air samples. Benzene and 1,3-butadiene were more abundant in live emergency fires, which caused higher exposures than the other studied situations. Both gaseous- and particle-associated PAHs were present on skin. The wrists seemed to be less well protected than the collarbone area. FFs and PFIs are exposed to several hazardous compounds during their work. Air exposures varied considerably between working scenarios. The observed exposures were substantially higher than urban background levels but well below Swedish OELs. The measured dermal PAH exposures were comparable to previously reported doses for US FFs but lower than the exposures reported for Swedish chimney sweeps.

Chalcophile chemistry for enhanced detection of copper in its compounds and minerals

Samples of elemental copper, upon laser irradiation under negative-ion LDI-MS conditions, do not generate noticeable signals for copper-bearing gaseous ions. In contrast, a several thousand-fold enhancement of the generated ion current was observed when freshly made mixtures of copper and sulfur powders were laser-ablated. Time-of-flight mass spectra recorded showed a range of peaks with m/z ratios extending to over m/z 8000, indicating the formation in situ of an array of Cu–S ion clusters by a chemical reaction that takes place between the two elements upon laser irradiation. Evidently, sulfur acts as a potent reactive matrix and generates at least three distinguishable series of ion clusters: Cu1Sx− (x = 2, 3, 4…), Cu2Sy− (y = 3, 4, 5…), and Cu3Sz− (z = 3, 4, 5…). Laser ablation of CuS alone did not produce signals beyond m/z 600. Some of the high-mass ions formed in this manner were isobaric; consequently, composite peaks were observed under low-resolution MS conditions. Under high-resolution conditions, however, we were able to separate and determine the composition of some isobaric mixtures. For example, the peak recorded at m/z 287 was resolved to two peaks that represented primarily the 63Cu265Cu32S3− and 63Cu32S7− ions. Intriguingly, the spectra recorded from many copper-containing minerals mixed with sulfur were remarkably similar to those acquired from copper-and-sulfur mixtures, which demonstrated that elemental sulfur has the ability to extract chemically bound copper even from its compounds, and form gas-phase Cu–S clusters of varying composition.

HILIC-Enabled 13C Metabolomics Strategies: Comparing Quantitative Precision and Spectral Accuracy of QTOF High- and QQQ Low-Resolution Mass Spectrometry.

Dynamic 13C-tracer-based flux analyses of in vivo reaction networks still require a continuous development of advanced quantification methods applying state-of-the-art mass spectrometry platforms. Utilizing alkaline HILIC chromatography, we adapt strategies for a systematic quantification study in non- and 13C-labeled multicomponent endogenous Corynebacterium glutamicum extracts by LC-QTOF high resolution (HRMS) and LC-QQQ tandem mass spectrometry (MS/MS). Without prior derivatization, a representative cross-section of 17 central carbon and anabolic key intermediates were analyzed with high selectivity and sensitivity under optimized ESI-MS settings. In column detection limits for the absolute quantification range were between 6.8–304.7 (QQQ) and 28.7–881.5 fmol (QTOF) with comparable linearities (3–5 orders of magnitude) and enhanced precision using QQQ-MRM detection. Tailor-made preparations of uniformly (U)13C-labeled cultivation extracts for isotope dilution mass spectrometry enabled the accurate quantification in complex sample matrices and extended linearities without effect on method parameters. Furthermore, evaluation of metabolite-specific m+1-to-m+0 ratios (ISR1:0) in non-labeled extracts exhibited sufficient methodical spectral accuracies with mean deviations of 3.89 ± 3.54% (QTOF) and 4.01 ± 3.01% (QQQ). Based on the excellent HILIC performance, conformity analysis of time-resolved isotopic enrichments in 13C-tracer experiments revealed sufficient spectral accuracy for QQQ-SIM detection. However, only QTOF-HRMS ensures determination of the full isotopologue space in complex matrices without mass interferences.

Strong evidence of drug-facilitated crimes by hair analysis using LC–MS/MS after micro-segmentation

Hair analysis can provide effective information to prove drug-facilitated crimes (DFCs). Herein, an analytical procedure for obtaining evidence of DFCs stronger than with conventional segmental hair analysis is demonstrated for an actual case. A victim reported to the police that, approximately 1 month earlier, she had consumed a drink, fallen asleep, and then been assaulted. Her hair strands were collected to examine whether drugs were detected from her hair. Drug screening by liquid chromatography–high-resolution mass spectrometry (LC–HR-MS) revealed a specific peak, derived from zolpidem, on the chromatogram obtained from the hair extract. Micro-segmental analysis using an internal temporal marker (ITM) was performed to estimate the day of zolpidem ingestion using sensitive LC–low-resolution tandem mass spectrometry (MS/MS). The victim ingested cold medicine as an ITM twice, with an interval of 21.0 days, to calculate the actual growth rate of her hair. Her hair strands were collected again 2 weeks after the second ITM ingestion. A hair strand was cut at 0.4-mm intervals, and the distribution curves of zolpidem and the ITM in a hair strand were plotted. The estimated day of zolpidem ingestion was consistent with the day of the incident that she had reported. The two-step hair analysis proved that she had ingested zolpidem on the day of the incident. The combination of drug screening by LC–HR-MS and determination of the day of drug ingestion using micro-segmental analysis by sensitive LC–MS/MS would be useful for elucidating the relationship between the drug and the incident when investigating DFCs.

Unified representation of high- and low-resolution spectra to facilitate application of mass spectrometric techniques in clinical practice

The majority of research in the biomedical sciences is carried out with the highest resolution accessible to the scientist, but, in the clinic, cost constraints necessitate the use of low-resolution devices. Here, we compare high- and low-resolution direct mass spectrometry profiling data and propose a simple pre-processing technique that makes high-resolution data suitable for the development of classification and regression techniques applicable to low-resolution data, while retaining high accuracy of analysis. This work demonstrates an approach to de-noising spectra to make the same representation for both high- and low-resolution spectra. This approach uses noise threshold detection based on the Tversky index, which compares spectra with different resolutions, and minimizes the percentage of resolution-specific peaks. The presented method provides an avenue for the development of analytical algorithms using high-resolution mass spectrometry data, while applying these algorithms in the clinic using low-resolution mass spectrometers.

IsoCor: isotope correction for high-resolution MS labeling experiments.

Mass spectrometry (MS) is widely used for isotopic studies of metabolism and other (bio)chemical processes. Quantitative applications in systems and synthetic biology require to correct the raw MS data for the contribution of naturally occurring isotopes. Several tools are available to correct low-resolution MS data, and recent developments made substantial improvements by introducing resolution-dependent correction methods, hence opening the way to the correction of high-resolution MS (HRMS) data. Nevertheless, current HRMS correction methods partly fail to determine which isotopic species are resolved from the tracer isotopologues and should thus be corrected. We present an updated version of our isotope correction software (IsoCor) with a novel correction algorithm which ensures to accurately exploit any chemical species with any isotopic tracer, at any MS resolution. IsoCor v2 also includes a novel graphical user interface for intuitive use by end-users and a command-line interface to streamline integration into existing pipelines. IsoCor v2 is implemented in Python 3 and was tested on Windows, Unix and MacOS platforms. The source code and the documentation are freely distributed under GPL3 license at https://github.com/MetaSys-LISBP/IsoCor/ and https://isocor.readthedocs.io/.

Rapid determination of isocitrate dehydrogenase mutation status of human gliomas by extraction nanoelectrospray using a miniature mass spectrometer.

Isocitrate dehydrogenase (IDH) I and II mutations in gliomas cause an abnormal accumulation of 2-hydroxyglutarate (2-HG) in these tumor cells. These mutations have potential prognostic value in that knowledge of the mutation status can lead to improved surgical resection. Information on mutation status obtained by immunohistochemistry or genomic analysis is not available during surgery. We report a rapid extraction nanoelectrospray ionization (nESI) method of determining 2-HG. This should allow the determination of IDH mutation status to be performed intraoperatively, within minutes, using a miniature mass spectrometer. This study demonstrates that the combination of tandem mass spectrometry with low-resolution mass spectrometry allows this analysis to be performed with confidence. Graphical Abstract.

The quantification of chlorinated paraffins in environmental samples by ultra-high-performance liquid chromatography coupled with Orbitrap Fusion Tribrid mass spectrometry

As high-production-volume chemicals, chlorinated paraffins (CPs) have raised an increasing environmental concern in recent years. However, their accurate analysis and quantification is still a huge challenge due to the high complexity of their technical formulations and the interference from CPs congeners and other polychlorinated products. In this study, a novel method for the simultaneous analysis of short-chain (SC) and medium-chain (MC) CPs in a single injection has been developed using ultra-high-performance liquid chromatography coupled with Orbitrap Fusion Tribrid mass spectrometry (UHPLC-Orbitrap Fusion TMS). Compared with other analytical methods for CPs, this novel method can greatly shorten the measurement time and provides a lower limit of detection. A high resolution of 120,000 FWHM was set to avoid the self-interference of CPs congeners and to eliminate interferences from chlorinated olefins (COs). Accuracies for SCCPs and MCCPs standards were evaluated at 75–103% and 83–118%, respectively. The developed method was further validated by determining CPs in sediment, soil, and indoor dust samples. This novel method gives higher CPs concentrations than those achieved by gas chromatography-electron capture negative ionization low-resolution mass spectrometry (GC-ECNI-LRMS), with factors of 1.1–12.5 for SCCPs and 0.7–2.7 for MCCPs, respectively. Some new CPs, such as C8Cl7-8 and C9Cl5-8, have been determined in soil samples for the first time, indicating great potential of this novel method for routine CP analysis in various environmental samples.

Synthesis and characterization of eight single chain length chlorinated paraffin standards and their use for quantification.

Quantification of chlorinated paraffins (CPs) via gas chromatography coupled with electron capture negative ionization low-resolution mass spectrometry (GC/ECNI-MS) is a very common practice, although the quality of the results has been disputed due to insufficient mass resolution and the strong impact of the degree of chlorination on the GC/ECNI-MS response. For further tests we synthesized eight single chain length CP standards (C10 -C17 ) with chlorine contents between 51.1% and 61.3%. The individual single chain length standards, 1 + 1 mixtures of two chain length standards and self-prepared mixtures of short-chain and medium-chain CPs were quantified by linear regression according to a previously reported method (method 1) as well as by exponential regression (method 2). Concentrations obtained from single chain length CP standards deviated between -74% and 152% from the target value. However, the error became smaller when self-prepared CP mixes with two and four chain lengths were analysed. For short-chain CP (SCCP) mixture analysis, both methods produced good results (<25% deviation from the target value). In the case of medium-chain CP (MCCP) mixtures, however, method 2 (17-34% deviation) was more accurate than method 1 (43-52% deviation). Both methods 1 and 2 are fit for GC/ECNI-MS analysis of SCCP mixtures, while the improved method 2 is recommended for quantification of MCCP mixtures.

Advantage of liquid chromatography with high-resolution mass spectrometry for the detection of the small and polar molecules trifluoroacetic acid and sulfamic acid.

This study addresses the selectivity of liquid chromatography with tandem mass spectrometry for the analysis of the polar analytes trifluoroacetic acid and sulfamic acid in water samples. Such analytes often lack sufficient retention in standard reversed-phase liquid chromatography and rarely produce mass spectrometry transition products of high diagnostic evidence by collision-induced dissociation. The chromatography based on an extra-dense bonding liquid chromatography column for trifluoroacetic acid and on hydrophilic interaction chromatography for sulfamic acid. This enabled sufficient retention of more than twice the void volume for both analytes. Liquid chromatography coupled to low-resolution mass spectrometry was compared with high-resolution mass spectrometry. The limits of quantification for direct injection analysis were determined to<0.05μg/L for trifluoroacetic acid and<0.5μg/L for sulfamic acid. Correction of matrix effects either by internal standards or the standard addition is strongly recommended as matrix effects may vary strongly. The concentrations determined for trifluoroacetic acid and sulfamic acid for real samples were comparable between low and high-resolution mass spectrometry. However, low-resolution mass spectrometry does not fulfill the identification criteria of the analytes following the European Commission council directive 96/23/EC or the SANTE/11945/2015. Since low-resolution mass spectrometry for these analytes may result in false-positive findings, such findings may be controlled by high-resolution mass spectrometry.