Analysis of complex drugs by comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry: detailed chemical description of the active pharmaceutical ingredient sodium bituminosulfonate and its process intermediates

The European pharmacopeia provides analytical methods for the chemical characterization of active pharmaceutical ingredients (APIs). However, the complexity of some APIs exceeds the limitations of the currently prevailing physicochemical methods. Sodium bituminosulfonate (SBS) is described by the collection of key parameters of generalizing criteria such as dry matter, sulfur and sodium content, and neutrality, but techniques to unravel the complexity on a molecular level are lacking. We present a study based on online derivatization with tetramethylammonium hydroxide in combination with comprehensive two-dimensional gas chromatography coupled to an electron ionization high-resolution time-of-flight mass spectrometer (GC × GC-HR-ToF–MS) for the chemical description of SBS as well as its process intermediates. The application of GC × GC allowed the comprehensive description of the chemical components in the API and the process intermediates for the first time. Furthermore, it was possible to classify peaks regarding their elemental and structural composition based on accurate mass information, elution behavior, and mass fragmentation pattern. This work demonstrates not only the general applicability, advantages but also limitations of GC × GC for the characterization of APIs for complex drugs. Graphical Abstract: [Figure not available: see fulltext.

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Entwicklung und Evaluation von innovativen Sammel-, Trenn- und Ionisationstechniken für die ultra-hochauflösende Massenspektrometrie: Analyse von Petroleum- und Verbrennungsaerosolproben

Novel approaches for the analysis of complex mixtures by high-resolution mass spectrometry are shown. A laser desorption/ionisation method for combustion particles was developed, whereas in electrospray ionisation a new dopant was introduced. For gas chromatography automatised algorithms providing more reliable data were developed. Coupling to thermal analysis enlarged the detectable species. This approach is evaluated for various complex mixtures, such as petrochemicals and biomass. Finally, a detailed chemical description of the most complex crude oil fraction, asphaltenes, could be shown

Detailed comparison of Xenon APPI (9.6/8.4 eV), Krypton APPI (10.6/10.0 eV), APCI, and APLI (266 nm) for gas chromatography high resolution mass spectrometry of standards and complex mixtures

Photoionisation schemes for mass spectrometry, either by laser or discharge lamps, have been widely examined and deployed. In this work, the ionisation characteristics of a Xenon discharge lamp (Xe-APPI, 9.6/8.4 eV) have been studied and compared to established ionisation schemes, such as atmospheric pressure chemical ionisation, atmospheric pressure photoionisation with a Krypton discharge lamp (Kr-APPI, 10.6/10 eV) and atmospheric pressure laser ionisation (266 nm). Addressing the gas-phase ionisation behaviour has been realised by gas chromatography coupling to high-resolution mass spectrometry without the usage of a dopant. For the multicomponent standard, it has been found that Xe-APPI is able to ionise a broad range of polycyclic aromatic hydrocarbons as well as their heteroatom-containing and alkylated derivatives. However, thiol and ester compounds could not be detected. Moreover, Xe-APPI revealed a high tendency to generate oxygenated artefact, most likely due to a VUV absorption band of oxygen at 148 nm. Beneficially, almost no chemical background, commonly caused by APCI or Kr-APPI due to column blood, plasticisers or impurities, is observed. This advantage is noteworthy for evolved gas analysis without pre-separation or for chromatographic co-elution. For the complex mixtures, Xe-APPI revealed the predominant generation of radical cations via direct photoionisation with a high selectivity towards aromatic core structures with low alkylation. Interestingly, both Xe-APPI and Kr-APPI could sensitively detect sterane cycloalkanes, validated by gas chromatographic retention. The narrowly ionised chemical space could let Xe-APPI find niche applications, e.g., for strongly contaminated samples to reduce the background

Comprehensive chemical description of pyrolysis chars from low-density polyethylene (LDPE) by thermal analysis hyphenated to different mass spectrometric approaches

The production and demand of plastics has drastically increased, with severe environmental impact. Waste incineration is not favored, and efficient recycling strategies are needed. Pyrolysis is a promising approaches but the nature of the residual char is not fully understood. To explore the value of this feedstock, thermal analysis with mass spectrometric detection is deployed. With soft photoionization, we were able to identify alkenes, dienes, and polycyclic aromatic hydrocarbons, which were emitted at four distinct mass loss events. Resonance-enhanced multiphoton ionization allows selectively addressing the aromatic constituents. Interestingly, we found an enrichment of UV-stabilizers, such as benzophenone, within the macromolecular nature. High-resolution mass spectrometry addressing the isobaric complexity and pyrolysis gas chromatography was used for structural elucidation. We hypothesize island- and archipelago-type structural motives comparable to asphaltenes but with almost no heteroatoms. The in-depth chemical description of plastic pyrolysis coke will be valuable knowledge in reactor design and material science

PyC2MC: an open-source software solution for visualization and treatment of high-resolution mass spectrometry data

Complex molecular mixtures are encountered in almost all research disciplines, such as biomedical ‘omics, petroleomics, and environmental sciences. State-of-the-art characterization of sample materials related to these fields, deploying high-end instrumentation, allow for gathering humongous quantity of molecular composition data. One established technological platform is ultrahigh-resolution mass spectrometry, e.g., Fourier-transform mass spectrometry (FT-MS). However, the huge amounts of data acquired in FT-MS often result in tedious data treatment and visualization. FT-MS analysis of complex matrices can easily lead to single mass spectra with more than 10,000 attributed unique molecular formulae. Sophisticated software solutions to conduct these treatment and visualization attempts from commercial and non-commercial origins exist. However, existing applications have distinct drawbacks, such as focusing on only one type of graphic representation, being unable to handle large datasets, or not being publicly available. In this respect, we developed a software, within the international complex matrices molecular characterization joint lab (IC2MC), named “python tools for complex matrices molecular characterization” (PyC2MC). This piece of software will be open-source and free to use. PyC2MC is written under python 3.9.7 and relies on well-known libraries such as pandas, NumPy, or SciPy. It is provided with a graphical user interface developed under PyQt5. The two options for execution, 1) user-friendly route with pre-packed executable file or 2) running the main python script through a Python interpreter, ensure a high applicability but also an open characteristic for further development by the community. Both are available on the GitHub platform (https://github.com/iC2MC/PyC2MC_viewer)

Accessing the Low-polar Molecular Composition of Boreal and Arctic Peat Burning Organic Aerosol via Thermal Analysis and Ultrahigh-Resolution Mass Spectrometry: Structural Motifs and Their Formation

Peatland fires emit organic carbon rich particulate matter into the atmosphere. Boreal and Arctic peatlands are becoming more vulnerable to wildfires, resulting in a need for better understanding of the emissions of these special fires. Extractable, non-, and low-polar organic aerosol species emitted from laboratory-based boreal and Arctic peat burning experiments are analyzed by direct-infusion atmospheric pressure photoionization (APPI) ultrahigh-resolution mass spectrometry (UHRMS) and compared to time-resolved APPI UHRMS evolved gas analysis from the thermal analysis of peat under inert nitrogen (pyrolysis) and oxidative atmosphere. The chemical composition is characterized on a molecular level, revealing abundant aromatic compounds that partially contain oxygen, nitrogen or sulfur and are formed at characteristic temperatures. Two main structural motifs are identified: single-core and multicore, and their temperature dependent formation is assigned to the thermal degradation of the lignocellulose building blocks and other parts of peat

Atmospheric aging increases the cytotoxicity of bare soot particles in BEAS-2B lung cells

Soot particles (SP) are ubiquitous components of atmospheric particulate matter and have been shown to cause various adverse health effects. In the atmosphere, freshly emitted SP can be coated by condensed low-volatility secondary organic and inorganic species. In addition, gas-phase oxidants may react with the surface of SP. Due to the chemical and physical resemblance of SP carbon backbone with polyaromatic hydrocarbon species and their potent oxidation products, we investigated the biological responses of BEAS-2B lung epithelial cells following exposure to fresh- and photochemically aged-SP at the air–liquid interface. A comprehensive physical and chemical aerosol characterization was performed to depict the atmospheric transformations of SP, showing that photochemical aging increased the organic carbon fraction and the oxidation state of the SP. RNA-sequencing and qPCR analysis showed varying gene expression profiles for fresh- and aged-SP. Exposure to aged-SP increased DNA damage, oxidative damage, and upregulation of NRF2-mediated oxidative stress response genes compared to fresh-SP. Furthermore, aged-SP augmented inflammatory cytokine secretion and activated AhR-response, as evidenced by increased expression of AhR-responsive genes. These results indicate that oxidative stress, inflammation, and DNA damage play a key role in the cytotoxicity of SP in BEAS-2B cells, where aging leads to higher toxic responses. Collectively, our results suggest that photochemical aging may increase SP toxicity through surface modifications that lead to an increased toxic response by activating different molecular pathways