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Understanding drug behavior within the skin, especially for photosensitive compounds, is crucial for developing effective and safe topical therapies. This study employs Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) and Liquid Chromatography-Mass Spectrometry (LC-MS/MS) to investigate the skin permeation and photostability of selumetinib, a MEK inhibitor used in treating type 1 neurofibromatosis (NF1). The highest amounts of selumetinib in the skin sections were obtained when using the gel formulation, suggesting that it is to be preferred to cream formulations to achieve higher permeation of the drug. Our study also revealed that selumetinib is amenable to photodegradation in ex vivo skin explants, and yields one main degradation product, whose degradation is likely triggered by hydrogen abstraction. MALDI-MSI results showed selumetinib and its degradation product concentrate in skin appendages, indicating these structures might serve as drug reservoirs, potentially prolonging retention and efficacy. This study demonstrates that combining MALDI-MSI with LC/MS-MS can highly contribute to the characterization of the fate of photosensitive compounds in the skin, an essential prerequisite to the development of compound-specific photoprotective measures. It will also pave the way for innovative topical delivery strategies for NF1 treatment. [ABSTRACT FROM AUTHOR]

The composition of dissolved organic matter of cloud water has been investigated through non-targeted high-resolution mass spectrometry on only a few samples that were mostly collected in the Northern Hemisphere in the USA, Europe and China. There remains, therefore, a lack of measurements for clouds located in the Southern Hemisphere, under tropical conditions and influenced by forest emissions. As a matter of fact, the comparison of the composition of clouds collected in different locations is challenging since the methodology for the analysis and data treatment is not standardized. In this work, the chemical composition of three samples collected at Réunion Island (REU) during the BIO-MAÏDO field campaign, in the Indian Ocean, with influences from marine, anthropogenic and biogenic (tropical) emissions, is investigated and compared to the chemical composition of samples collected at the Puy de Dôme (PUY) observatory in France. The same methodology of analysis and data treatment was employed, producing a unique dataset for the investigation of the molecular composition of organic matter in cloud water. Besides the analysis of elemental composition, we investigated the carbon oxidation state (OSC) of dissolved organic matter, finding that overall samples collected at PUY are more oxidized than those collected at REU. Molecular formulas were also classified based on stoichiometric elemental ratios, showing the high frequency and abundance of reduced organic compounds, classified as lipids (LipidC), in this matrix, which led to a search for terpene oxidation products in cloud water samples. To better discriminate between samples collected at PUY and REU, statistical analysis (principal component analysis and agglomerative hierarchical clustering) was performed on the ensemble of molecular formulas and their intensities. Samples collected at REU have a different composition from samples collected at PUY, which is mainly linked to different primary sources, the processing of organic matter in cloud water and the influence of different primary emissions at the two locations. [ABSTRACT FROM AUTHOR]

The composition of cloud water dissolved organic matter has been investigated through non-targeted high resolution mass spectrometry only on few samples, mostly collected in the Northern hemisphere, in USA, Europe and China. Nevertheless, there is a lack of measurements for clouds located in the Southern Hemisphere, under tropical conditions and influenced by forest emissions. Moreover, the comparison of the composition of cloud samples collected in different locations is not trivial, since the methodology for the analysis and data treatment are not standardized. In this work, the chemical composition of three samples collected at Reunion Island (REU) during the BIO-MAÏDO field campaign, in the Indian Ocean, with influences from marine, anthropogenic and biogenic (tropical) emissions is investigated and compared to the chemical composition of samples collected at the puy de Dôme (PUY) observatory, in France. The same methodology of analysis and data treatment was employed, producing a unique dataset for the investigation of molecular composition of organic matter in cloud water. Besides the analysis of elemental composition, we investigated the carbon oxidation state (OSC) of dissolved organic matter, finding that overall samples collected at PUY are more oxidized than those collected at REU. Molecular formulas were also classified based on stoichiometric elemental ratios, showing the high frequency and abundance of reduced organic compounds, classified as lipids (LipidC), in this matrix, which led to search for terpenes oxidation products in cloud water samples. To better discriminate between samples collected at PUY and at REU, statistical analysis (principal component analysis and agglomerative hierarchical clustering) was performed on the ensemble of molecular formulas and their intensities. Samples collected at REU, have a different composition from samples collected at PUY, mainly linked to the processing of organic matter in cloud water, but also to the influence of different primary emissions at the two locations. [ABSTRACT FROM AUTHOR]

Ion cyclotron resonance (ICR) cells provide stability and coherence of ion oscillations in crossed electric and magnetic fields over extended periods of time. Using the Fourier transform enables precise measurements of ion oscillation frequencies. These precisely measured frequencies are converted into highly accurate mass‐to‐charge ratios of the analyte ions by calibration procedures. In terms of resolution and mass accuracy, Fourier transform ICR mass spectrometry (FT‐ICR MS) offers the highest performance of any MS technology. This is reflected in its wide range of applications. However, in the most challenging MS application, for example, imaging, enhancements in the mass accuracy of fluctuating ion fluxes are required to continue advancing the field. One approach is to shift the ion signal power into the peak corresponding to the true cyclotron frequency instead of the reduced cyclotron frequency peak. The benefits of measuring the true cyclotron frequency include increased tolerance to electric fields within the ICR cell, which enhances frequency measurement precision. As a result, many attempts to implement this mode of FT‐ICR MS operation have occurred. Examples of true cyclotron frequency measurements include detection of magnetron inter‐harmonics of the reduced cyclotron frequency (i.e., the sidebands), trapping field‐free (i.e., screened) ICR cells, and hyperbolic ICR cells with quadrupolar ion detection. More recently, ICR cells with spatially distributed ion clouds have demonstrated attractive performance characteristics for true cyclotron frequency ion detection. Here, we review the corresponding developments in FT‐ICR MS over the past 40 years. [ABSTRACT FROM AUTHOR]

The UV–vis photodegradation of α-tocopherol was investigated in a model system and in a cosmetic emulsion. Both gas chromatography coupled with tandem mass spectrometry (GC–MS/MS) and high performance liquid chromatography coupled with ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (LC-UHR-MS) were used for photoproducts structural identification. Nine photoproduct families were detected and identified based on their mass spectra and additional experiments with α-tocopherol-d 9 ; phototransformation mechanisms were postulated to rationalize their formation under irradiation. In silico QSAR (Quantitative Structure Activity Relationship) toxicity predictions were conducted with the Toxicity Estimation Software Tool (T.E.S.T.). Low oral rat LD50 values of 466.78 mg kg −1 and 467.9 mg kg −1 were predicted for some photoproducts, indicating a potential toxicity more than 10 times greater that of α-tocopherol (5742.54 mg kg −1 ). In vitro assays on Vibrio fischeri bacteria showed that the global ecotoxicity of the α-tocopherol solution significantly increases with irradiation time. One identified product should contribute to this ecotoxicity enhancement since in silico estimations for D. magna provide a LC50 value 4 times lower than that of the parent molecule. [ABSTRACT FROM AUTHOR]

Gas-phase infrared photodissociation spectroscopy is reported for the microsolvated [Mn(ClO4)(H2O) n ]+ and [Mn2(ClO4)3(H2O) n ]+ complexes from n = 2 to 5. Electrosprayed ions are isolated in an ion-trap where they are photodissociated. The 2600–3800 cm−1 spectral region associated with the OH stretching mode is scanned with a relatively low-power infrared table-top laser, which is used in combination with a CO2 laser to enhance the photofragmentation yield of these strongly bound ions. Hydrogen bonding is evidenced by a relatively broad band red-shifted from the free OH region. Band assignment based on quantum chemical calculations suggest that there is formation of water–perchlorate hydrogen bond within the first coordination shell of high-spin Mn(II). Although the observed spectral features are also compatible with the formation of structures with double-acceptor water in the second shell, these structures are found relatively high in energy compared with structures with all water directly bound to manganese. Using the highly intense IR beam of the free electron laser CLIO in the 800–1700 cm−1, we were also able to characterize the coordination mode (η2) of perchlorate for two clusters. The comparison of experimental and calculated spectra suggests that the perchlorate Cl–O stretches are unexpectedly underestimated at the B3LYP level, while they are correctly described at the MP2 level allowing for spectral assignment. [Copyright &y& Elsevier]

In untargeted metabolomics, the unambiguous identification of metabolites remains a major challenge. This requires high-quality spectral libraries for reliable metabolite identification, which is essential for translating metabolomics data into meaningful biological information. Several attempts have been made to generate reproducible product ion spectra (PIS) under a low collision energy (ELab) regime and nonresonant collisional conditions but have not fully succeeded. We examined the ERMS (energy-resolved mass spectrometry) breakdown curves of two lipo-amino acids and showed the possibility to highlight "singular points", called descriptors hereafter (linked to respective ELab depending on the instrument), for each of the monomodal product ion profiles. Using several instruments based on different technologies, the PIS recorded at these specific ELab sites shows remarkable similarities. The descriptors appeared as being independent of the fragmentation mechanisms and can be used to overcome the main instrumental effects that limit the interoperability of spectral libraries. This proof-of-concept study, performed on two particular lipo-amino acids, demonstrates the high potential of ERMS-derived information to determine the instrument-specific ELab at which PIS recorded in nonresonant conditions become highly similar and instrument-independent, thus comparable across platforms. This innovative but straightforward approach could help remove some of the obstacles to metabolite identification in nontargeted metabolomics, putting an end to a challenging chimera. [ABSTRACT FROM AUTHOR]

Perfluorocarbons, a class of fully fluorinated compounds, are highly persistent and toxic pollutants that are receiving increasing attention due to their widespread environmental distribution. In this study, attention was focused on one compound in particular, namely, perfluorooctanoic acid (PFOA). The first investigation of the UV/VUV photochemistry of the PFOA anion in the gas phase by action spectroscopy of selected ions is reported. Two main relaxation channels were identified: photodissociation and photodetachment. Absolute cross sections for the individual observed processes were measured. DFT calculations and natural transition orbital analysis were carried out to help in the interpretation of the experimental results., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This work aims to improve the computation of infrared spectra of gas-phase cations using DFT methods. Experimental infrared multiple photon dissociation (IRMPD) spectra for ten Zn and Ru organometallic complexes have been used to provide reference data for 64 vibrational modes in the 900-2000 cm -1 range. The accuracy of the IR vibrational frequencies predicted for these bands has been assessed over five DFT functionals and three basis sets. The functionals include the popular B3LYP and M06-2X hybrids and the range-separated hybrids (RSH) CAM-B3LYP, LC-BLYP, and ωB97X-D. B3LYP gives the best mean absolute error (MAE) and root-mean-square error (RMSE) values of 7.1 and 9.6 cm -1 , whilst the best RSH functional, ωB97X-D, gives 12.8 and 16.6 cm -1 , respectively. Using linear correlations instead of scaling factors improves the prediction accuracy significantly for all functionals. Experimental and computed spectra for a single complex can show significant differences even when the molecular structure is calculated correctly, and a means of defining confidence limits for any given computed structure is also provided., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)