Application Of High-resolution Mass Spectrometry Research Articles

Enhancement of oil forensic methodology through the addition of polycyclic aromatic nitrogen heterocycle biomarkers for diagnostic ratios

Current oil spill forensic identification of source oils relies upon hydrocarbon biomarkers resistant to weathering. This international technique was developed by the European Committee for Standardization (CEN), under EN 15522–2 Oil Spill Identification guidelines. The number of biomarkers have expanded at pace with technological advances, while distinguishing new biomarkers becomes more challenging due to interference of isobaric compounds, matrix effects, and high cost of weathering experiments. Application of high-resolution mass spectrometry enabled exploration of potential polycyclic aromatic nitrogen heterocycle (PANH) oil biomarkers. The instrumentation showed reduction in isobaric and matrix interferences, allowing for identification of low-level PANH and alkylated PANHs (APANHs). Weathered oil samples, obtained from a marine microcosm weathering experiment, enabled comparison with source oils to identify new, stable forensic biomarkers. This study highlighted eight new APANH diagnostic ratios that expanded the biomarker suite, increasing the confidence for identifying highly weathered oils back to their source oil.

Application of High-Resolution Mass Spectrometry to Evaluate UV-Sulfite-Induced Transformations of Per- and Polyfluoroalkyl Substances (PFASs) in Aqueous Film-Forming Foam (AFFF).

UV-sulfite has been shown to effectively degrade per- and polyfluoroalkyl substances (PFASs) in single-solute experiments. We recently reported treatment of 15 PFASs, including perfluoroalkyl sulfonic acids (PFSAs), perfluoroalkyl carboxylic acids (PFCAs), and fluorotelomer sulfonic acids (FTSs), detected in aqueous film-forming foam (AFFF) using high-resolution liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) targeted analysis. Here, we extend the analysis within those original reaction solutions to include the wider set of PFASs in AFFF for which reactivity is largely unknown by applying recently established LC-QTOF-MS suspect screening and semiquantitative analysis protocols. Sixty-eight additional PFASs were detected (15 targeted + 68 suspect screening = 83 PFASs) with semiquantitative analysis, and their behavior was binned on the basis of (1) detection in untreated AFFF, (2) PFAS photogeneration, and (3) reactivity. These 68 structures account for an additional 20% of the total fluorine content in the AFFF (targeted + suspect screening = 57% of total fluorine content). Structure-reactivity trends were also revealed. During treatment, transformations of highly reactive structures containing sulfonamide (-SO2N-) and reduced sulfur groups (e.g., -S- and -SO-) adjacent to the perfluoroalkyl [F(CF2)n-] or fluorotelomer [F(CF2)n(CH2)2-] chain are likely sources of PFCA, PFSA, and FTS generation previously reported during the early stages of reactions. The results also show the character of headgroup moieties adjacent to the F(CF2)n-/F(CF2)n(CH2)2- chain (e.g., sulfur oxidation state, sulfonamide type, and carboxylic acids) and substitution along the F(CF2)n- chain (e.g., H-, ketone, and ether) together may determine chain length-dependent reactivity trends. The results highlight the importance of monitoring PFASs outside conventional targeted analytical methodologies.

Connecting chemical exposome to human health using high-resolution mass spectrometry-based biomonitoring: Recent advances and future perspectives.

Compared with the rapid advances in genomics leading to broad understanding of human disease, the linkage between chemical exposome and diseases is still under investigation. High-resolution mass spectrometry (HRMS) is expected to accelerate the process via relatively accurate and precise biomonitoring of human exposome. This review covers recent advancements in biomonitoring of exposed environmental chemicals (chemical exposome) using HRMSdescribed in the 124 articles that resulted from a systematic literature search on Medline and Web of Science databases. The analytical strategic aspects, including the selection of specimens, sample preparation, instrumentation, untargeted versus targeted analysis, and workflows for MS-based biomonitoring to explore the environmental chemical space of human exposome, are deliberated. Applications of HRMS in human exposome investigation are presented by biomonitoring (1) exposed chemical compounds and their biotransformation products; (2) DNA/protein adducts; and (3) endogenous compound perturbations. Challenges and future perspectives are also discussed.

Suspect and non-targeted screening-based human biomonitoring identified 74 biomarkers of exposure in urine of Slovenian children

Human exposure to organic contaminants is widespread. Many of these contaminants show adverse health effects on human population. Human biomonitoring (HBM) follows the levels and the distribution of biomarkers of exposure (BoE), but it is usually done in a targeted manner. Suspect and non-targeted screening (SS/NTS) tend to find BoE in an agnostic way, without preselection of compounds, and include finding evidence of exposure to predicted, unpredicted known and unknown chemicals.This study describes the application of high-resolution mass spectrometry (HRMS)-based SS/NTS workflow for revealing organic contaminants in urine of a cohort of 200 children from Slovenia, aged 6–9 years. The children originated from two regions, urban and rural, and the latter were sampled in two time periods, summer and winter. We tentatively identified 74 BoE at the confidence levels of 2 and 3. These BoE belong to several classes of pharmaceuticals, personal care products, plasticizers and plastic related products, volatile organic compounds, nicotine, caffeine and pesticides. The risk of three pesticides, atrazine, amitraz and diazinon is of particular concern since their use was limited in the EU. Among BoE we tentatively identified compounds that have not yet been monitored in HBM schemes and demonstrate limited exposure data, such as bisphenol G, polyethylene glycols and their ethers. Furthermore, 7 compounds with unknown use and sources of exposure were tentatively identified, either indicating the entry of new chemicals into the market, or their metabolites and transformation products. Interestingly, several BoE showed location and time dependency.Globally, this study presents high-throughput approach to SS/NTS for HBM. The results shed a light on the exposure of Slovenian children and raise questions on potential adverse health effects of such mixtures on this vulnerable population.

Application of Liquid Chromatography-high Resolution Time-of-flight Mass Spectrometry in the Detection of Raw Milk and Dairy Products

Milk and dairy products are more and more popular with consumers due to their various nutrients, and their quality and safety issues have always been concerned. At present, the quality of milk and dairy products has become the core competitiveness of enterprises' future consumption and promotion, among which food additives and illegal additives, agricultural and veterinary drug residues, plasticizer and other exogenous risk substances are the focus of social attention. Therefore, it is of great practical significance and application value to establish the screening and analysis methods of exogenous risk substances in milk and dairy products. However, the ingredients of milk and dairy products are complex, and the exogenous risk substances are mostly small molecules, with low content and not easy to detect. Therefore, the instrument is required to have a very high selectivity and a super-high quality precision. Time-of-flight mass spectrometry is a high-resolution mass spectrometry, which can easily and quickly complete the rapid screening and identification of target compounds and unknown compounds, reduce the probability of "false positive" occurrence, and can analyze hundreds of compounds in a testing process, which can realize the accurate quantification and screening of veterinary drugs in milk. This paper mainly expounds the application of high-resolution mass spectrometry in exogenous risk material screening and adulterated substance analysis in milk and dairy products, and briefly analyzes its application prospects.

Direct coupling of MEPS to ESI-QqTOF-MS for the simultaneous analysis of tricyclic antidepressants and benzodiazepines in postmortem blood

The combination of chromatography and mass spectrometry is the golden standard in forensic sciences. Although this approach provides high sensitivity and selectivity levels, it is time-consuming. The circumvention of the chromatography can increase the sample throughput, but the selectivity must be compensated by using a selectivity enhanced instrumental technique, such as high-resolution mass spectrometry (HRMS), and designing an appropriate sample preparation step. Microextraction by packed sorbent (MEPS) has proven potential to treat complex biological samples in a fast and reproducible way. It allows processing low sample volumes, remaining a green procedure due to low solvent consumption. This article presents the direct coupling of a MEPS syringe to the electrospray ionization source (ESI) of a quadrupole time-of-flight mass spectrometer (QqTOF) using an infusion pump for sample introduction, as a proof of concept. The developed method was validated for the simultaneous analysis of benzodiazepines and tricyclic antidepressants in postmortem blood samples. Limits of quantification (LOQ) were between 25 and 50 ng mL−1 for all compounds. Accuracy and precision were evaluated at three concentration levels (50, 125 and 350 ng mL−1) and expressed in terms of relative error (%RE) and relative standard deviation (%RSD), respectively. Both parameters were better than 20% for the lower concentration evaluated and better than 15% for the other two concentration levels. The developed method was used to analyze authentic postmortem blood samples, to test the applicability in the forensic toxicological context. The results are in agreement with the data provided by the medico-legal services. Also, the application of HRMS has allowed the identification of unexpected targets in the samples.

Advances in mass spectrometry for molecular characterization of oil sands naphthenic acids and process chemicals in wetlands

Advances in mass spectrometry in the authors’ and key collaborators’ research are reviewed for analysis of oil sands naphthenic acids fraction compounds (NAFCs) and industrial process chemicals, sulfolane and alkanolamines, in wetlands. Focus is given to developments of analyses of NAFCs in constructed wetland treatment systems and natural wetlands in the Athabasca oil sands region, Alberta, Canada. The analytical developments are applied to show the utility of wetlands to sequester and oxidize oil sands naphthenic acids. The advancements in molecular characterization led to the first application of high-resolution mass spectrometry (Fourier transform ion-cyclotron resonance and Orbitrap mass spectrometry) for elucidation of toxic mono- and di-carboxylic NAFCs in oil sands environmental samples. Key findings reveal that oil sands NAFCs are not limited to saturated structures but contain a diverse range of components, many of which contain S, N, heteroatomic species and aromatic species. Other developments of mass spectrometry methods for industrial process chemicals show for the first time that the completely water-miscible chemical, sulfolane, translocate to upper portions of cattails at natural wetland sites in the Canadian environment. Likewise, wetland-plant mediated changes of complex mixtures of alkanolamines were revealed based on the coupling of ion chromatography mass spectrometry and ultrahigh resolution mass spectrometry. The advances in mass spectrometry are of particular benefit to Canada, for development of soil and water quality guidelines for oil sands NAFCs and process chemicals. In turn, the water quality guidelines serve to protect Canadian aquatic environments.

Material characterization of polyamide 12 and related agents used in the multi-jet fusion process: complementary application of high-resolution mass spectrometry and other advanced instrumental techniques

The powder bed-based 3D printing process called multi-jet fusion from HP is used in various industries for different applications. A polymer powder, the so-called fusing and detailing agents, and an IR source are needed. These novel materials offer some challenges for analytical characterization. High-resolution mass spectrometry in combination with a data base search was used as a tool for comprehensive characterization of the agents, the methanol extract of new polyamide 12 powder, and the methanol extract of a grinded 3D printed part. In addition, thermogravimetric studies were carried out. Besides biocides and substances containing ethoxy units, 2-pyrrolidone and triethylene glycol were identified as organic solvents in the agents. The detailing agent contained 3.7% of 2-pyrrolidone and 11.1% of triethylene glycol. The fusing agent contained 18.7% of 2-pyrrolidone and 8.4% of triethylene glycol. Based on the agents’ different functionalities, the water content of the detailing agent was 18% higher as compared to the fusing agent. In addition, the fusing agent contained a carbon black amount of 5.2%. The methanol extract of new polyamide 12 powder contained remaining monomer and oligomer compounds, as well as the oxidation stabilizer Irganox 1098. In the methanol extract of the grinded 3D printed part the cyclic and linear monomer, oligomers, and oxidation stabilizer were found. Moreover, ingredients of the agents were detected. Residues of 2-pyrrolidone, triethylene glycol, 3-benzisothiazolinone, and substances containing ethoxy units were identified in the methanol extract of the grinded 3D printed part. In contrast, no 2-methyl-4-isothiazolin-3-one was observed.Graphical abstract

Application of High-Resolution Mass Spectrometry and a Theoretical Model to the Quantification of Multifunctional Carbonyls and Organic Acids in e-Cigarette Aerosol.

Electronic (e-) cigarette aerosol (particle and gas) is a complex mixture of chemicals, of which the profile is highly dependent on device operating parameters and e-liquid flavor formulation. The thermal degradation of the e-liquid solvents propylene glycol and glycerol often generates multifunctional carbonyls that are challenging to quantify because of unavailability of standards. We developed a theoretical method to calculate the relative electrospray ionization sensitivities of hydrazones of organic acids and carbonyls with 2,4-dinitrophenylhydrazine based on their gas-phase basicities (ΔGdeprotonation). This method enabled quantification by high-performance liquid chromatography-high-resolution mass spectrometry HPLC-HRMS in the absence of chemical standards. Accurate mass and tandem multistage MS (MSn) were used for structure identification of vaping products. We quantified five simple carbonyls, six hydroxycarbonyls, four dicarbonyls, three acids, and one phenolic carbonyl in the e-cigarette aerosol with Classic Tobacco flavor. Our results suggest that hydroxycarbonyls, such as hydroxyacetone, lactaldehyde, and dihydroxyacetone can be significant components in e-cigarette aerosols but have received less attention in the literature and have poorly understood health effects. The data support the radical-mediated e-liquid thermal degradation scheme that has been previously proposed and emphasize the need for more research on the chemistry and toxicology of the complex product formation in e-cigarette aerosols.

Applications of High-Resolution Mass Spectrometry in Determination of Chlorinated Paraffins

Abstract Chlorinated paraffins (CPs) are a new class of persistent organic pollutants and have aroused great concern of many environmental scientists, due to their ubiquity in various environmental media and biotas. Given their relative low levels in environmental samples, CPs need to be enriched and cleaned up before instrumental analysis. CPs consist of thousands of congeners and isomers, thus posing grand challenges to eliminate the mass interference by homologues and other organohalogen compounds during instrumental examination. Fortunately, high-resolution mass spectrometry (HRMS) owns the powerful ability to solve this key problem owing to its high mass resolution. This review introduces the methods of pretreatment and instrumental analysis of CPs-containing samples in the environment, mainly illustrating the application of gas chromatography and liquid chromatography coupled with HRMS (i.e. GC-HRMS and LC-HRMS). The existing issues and prospects of future study are also discussed.

Applications of High-Resolution Mass Spectrometry in Studies of Brown Carbon

Abstract Brown carbon is a hotspot in the field of atmospheric carbonaceous aerosol research. It has significant influence on regional radiative forcing and exerts climatic effects due to its apparent absorbance in the near ultraviolet-visible region. Brown carbon is mainly derived from incomplete combustion of biomass or coal, as well as secondary sources, such as a series of atmospheric photochemical reactions from volatile organic compounds. Although the composition of brown carbon is complex, high-resolution mass spectrometry, with its ultra-high mass resolution and precision, enables elucidation of the characteristics of the organic components of brown carbon at the molecular level. Here, high-resolution mass spectrometry combined with traditional analytical methods was used for the study of brown carbon. The development of high-resolution mass spectrometry for brown carbon separation is reviewed, as well as compositional analysis, source apportionment, and formation mechanism of brown carbon based on high-resolution data. In addition, the issues and prospects for the application of high-resolution mass spectrometry to evaluate brown carbon are discussed.

Sensitive determination of nine anticoagulant rodenticides in blood by high resolution mass spectrometry with supported liquid extraction pretreatment

Anticoagulant rodenticides (ARs) have been widely used for controlling rodents in agriculture and households. It often occurs that non-target animals are poisoned by ARs. Also, the abuse of ARs has been often encountered in poisoning and suicide cases. Herein we report the determination of nine commonly used ARs by high resolution mass spectrometry (HRMS) with supported liquid extraction (SLE) pretreatment. The factors affecting SLE (elution solvents and pH values) were systematically tested and optimized. The application of parallel reaction monitoring (PRM) mode led to the highest sensitivity obtained for these compounds, with LODs ranging for 0.006–0.02ng/mL. Reasonable extraction recoveries for all the analytes were obtained ranging in 73.9%–110.7%. Good precision was achieved for the spiked blood samples, with intra-day RSD ranging in 5.0%–9.2% and inter-day RSD ranging in 6.3%–10.5%. The values of ME ranged in 82.9%–103.2% for QC sample, which are reasonable. The application of HRMS in PRM mode also resulted in high selectivity. The method was applied to the detection and quantification of ARs in blood samples from real forensic cases. This methodology possesses high potential for determination of rodenticides in clinical and forensic cases.

Meet the Editors: Dietrich A. Volmer

Meet the Editors: Dietrich A. Volmer

Application of gas and liquid chromatography coupled to time-of-flight mass spectrometry in pesticides: Multiresidue analysis.

Analysis of pesticide residues in water and food matrices is an active research area closely related to food safety and environmental issues. In this aspect mass spectrometry (MS) coupled to gas chromatography (GC) and liquid chromatography (LC) has been increasingly used in the analysis of pesticide residues in water and food. The increasing interest in application of high-resolution mass spectrometry with time-of-flight (TOF) and hybrid triple quadrupole TOF in pesticide analysis is due to its capability of performing both targeted and nontargeted analysis. This article discusses an overview of the application of GC-TOF-MS and LC-TOF-MS in water and food matrices.

Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review.

The proliferation of new psychoactive substances (NPS) in recent years has resulted in the development of numerous analytical methods for the detection and identification of known and unknown NPS derivatives. High-resolution mass spectrometry (HRMS) has been identified as the method of choice for broad screening of NPS in a wide range of analytical contexts because of its ability to measure accurate masses using data-independent acquisition (DIA) techniques. Additionally, it has shown promise for non-targeted screening strategies that have been developed in order to detect and identify novel analogues without the need for certified reference materials (CRMs) or comprehensive mass spectral libraries. This paper reviews the applications of HRMS for the analysis of NPS in forensic drug chemistry and analytical toxicology. It provides an overview of the sample preparation procedures in addition to data acquisition, instrumental analysis, and data processing techniques. Furthermore, it gives an overview of the current state of non-targeted screening strategies with discussion on future directions and perspectives of this technique. Graphical Abstract Missing the bullseye - a graphical respresentation of non-targeted screening. Image courtesy of Christian Alonzo.

In-Depth Lipidomic Analysis of Molecular Species of Triacylglycerides, Diacylglycerides, Glycerophospholipids, and Sphingolipids of Buttermilk by GC-MS/FID, HPLC-ELSD, and UPLC-QToF-MS.

Buttermilk, a byproduct of butter manufacturing, has gained considerable attention due to its high concentration of polar lipids as phospho- and sphingolipids from the milk fat globule membrane (MFGM). These polar lipids (PLs) are essential components of all cellular membranes and exert a variety of indispensable metabolic, neurological, and intracellular signaling processes. Despite its importance, there are few research studies that report a comprehensive characterization of the lipid molecular species of MFGM that could contribute to a better understanding of their putative healthful activities. In this study, procedures such as pressurized liquid extraction of polar and nonpolar lipids and their fractionation by flash chromatography have been carried out. The obtained fractions were submitted to an exhaustive characterization from a lipidomic point of view. The characterization includes new data about the identification and quantification of triacylglycerides (TAG), diacylglycerides (DAG), and phospho- and sphingolipids using different chromatographic techniques. The fatty acid profile was comparable to that of the milk fat but with a highly diverse composition of fatty acids. Molecular species have also been determined by using ultra-high performance liquid chromatography/quadruple-time-of-flight mass spectrometry (UPLC/QToF-MS). The TAG (16:0/16:0/6:0) and TAG (16:0/16:0/8:0) were the predominant saturated TAG species and TAG (14:0/18:1/16:0) and TAG (16:0/16:0/18:1) presented the highest content of monounsaturated TAG species. Furthermore; over 30 molecular species of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI) could be identified within PL, with PC (16:0/18:1) being the most abundant species. Whereas C16:0 was found to be the preferred FA in TAGs, it was C18:1 in PLs. Several ganglioside species have also been characterized with d18:1 ceramide moiety and secondary acyl chains ranging from C20:0 to C26:1. This approach could broaden the applications of high-resolution mass spectrometry for a better understanding of the role of MFGM and its functionality.

Identification of Oxidative Degradation Products of Lansoprazole by Using High Resolution Mass Spectrometry Spectral Data

The study focused on the application of high-resolution mass spectrometry for the identification of impurities in pharmaceutical small molecules. A high-performance liquid chromatography (HPLC) coupled high resolution mass spectrometer (HRMS) was used for identification of oxidative degradation impurities (DIs) of lansoprazole. The utilization of HRMS facilitates to determine the accurate mass of impurities and their fragment/product ions. A fast mass spectrometer (MS) compatible reverse phase chromatography method was used to investigate the oxidative stressed impurities. HPLC column; C18 (50 × 4.6 mm, 3.5 μm) was used with gradient elution. Spectral data acquired using information dependent acquisition (IDA) with real time dynamic background subtraction algorithm (DBS). Three oxidative impurities: DI-I (m/z 386.0781), DI-II (m/z 402.0734) and DI-III (m/z 386.0785), was observed during this study; interpretation of high resolution spectral data of all three impurities was carried out; elemental composition and molecular structure was proposed for major fragments. In this study mass error was found ≤7.7 parts per million (ppm).

High-resolution mass spectrometry in toxicology: current status and future perspectives.

This paper reviews high-resolution mass spectrometry (HRMS) approaches using time-of-flight or Orbitrap techniques for research and application in various toxicology fields, particularly in clinical toxicology and forensic toxicology published since 2013 and referenced in PubMed. In the introduction, an overview on applications of HRMS in various toxicology fields is given with reference to current review articles. Papers concerning HRMS in metabolism, screening, and quantification of pharmaceuticals, drugs of abuse, and toxins in human body samples are critically reviewed. Finally, a discussion on advantages as well as limitations and future perspectives of these methods is included.

Application of high-resolution mass spectrometry to determination of baclofen in a case of fatal intoxication.

The study focused on the application of high-resolution mass spectrometry (HRMS) to postmortem toxicological analysis. Fast and simple sample preparation involved precipitation with acetonitrile, removal of phospholipids using special columns and filtration. Qualitative and quantitative analyses were performed using ultra-performance liquid chromatography coupled with quadrupole time-of–flight mass spectrometry. The method was validated by determining the limit of quantification, precision, recovery and matrix effect. The use of a high-resolution spectrometer allowed us to determine the precise masses of the fragments of interest and to suggest the fragmentation pathway of baclofen. The usefulness, effectiveness and assets of the procedure were confirmed by an authentic case of a 25-year-old woman fatally intoxicated with baclofen who was found dead in her apartment. Toxicological analysis of postmortem blood samples demonstrated that the baclofen concentration was 30.7 μg/mL. In only one published case describing fatal baclofen intoxication were no other xenobiotics (that could interact with baclofen) found. To our knowledge, this is the first report dealing with analysis of baclofen by HRMS.

Advances in Lignite Extraction and Conversion under Mild Conditions

Lignites are abundant coal resources, but they are low-quality fuel for direct combustion because of their high moisture content, high ash yield, and low calorific value. Upgrading technologies for lignites such as drying and pyrolysis have been widely investigated. Lignite conversion under mild conditions for producing ash-free coals, value-added chemicals, and/or liquid fuels also deserves attention. This paper reviews recent developments in extraction and mild conversion of lignites. The related techniques, including sequential extraction, thermal dissolution, mild oxidation, and catalytic hydroconversion of lignites, are described in detail. In addition, the application of high-resolution mass spectrometry in determining lignite-derived products is presented. Future investigations on efficient utilization of lignites are also suggested.