The Chemical Weapons Convention (CWC) is a science-based international treaty for the disarmament and non-proliferation of chemical weapons. However, reference Orgaization for prohibition of chemical weapons (OPCW) central analytical database (OCAD) of structures with mass spectra (MS) and retention indices (RI) includes only minor part of all possible chemical species defined in the Schedules of CWC. In this work we employed OCAD in silico augmentation based on chemoinformatics approach for chemical structures enumeration, MS data generation based on message passing neural network and based on P-alkyl molecular pairs RI prediction to support the verification activities as provided for in the CWC. Enumerated 879 noncyclic and 5270 monocyclic alcohols became the basis for generating hundreds of thousands molecules of Schedule 1 toxic chemicals like Sarin, Tabun, VX and Novichok. Trained on ordinary and neutral loss electron ionization mass spectrometry (EI-MS) a message-passing neural network (MPNN) outperformed other quantum chemistry and machine learning methods. Generated by this MPNN in silico EI-MS are very similar to the library's spectra and allowed to reach desired match factor above 800 within a scale of 0–1000. Statistical data for molecular pairs based on P-alkyl fragments was collected and used to predict RIs within desired 20 RI window for some toxic chemicals of Schedule 1.A.01, for which in the current OCAD version RIs are absent.

For thousands years Ephedrae herba has been used in traditional Chinese herbal medicine. Its main bioactive constituents are ephedrine and pseudoephedrine. Nowadays, these alkaloids have found application in various clinical treatments, as sports-enhancing drugs and for the illicit production of amphetamine-like drugs. Ephedrine and pseudoephedrine are diastereomers, and because of their high polarity and similar pKa values, their chromatographic separation may be a challenge. In this study a possible application of direct infusion mass spectrometry and direct infusion tandem mass spectrometry has been proposed for differentiation of ephedrine and pseudoephedrine as well as the relative determination of the contents of these compounds in a mixture. At low collision energy condition, the ratio of relative abundances of ions [M+H–H2O]+ and [M+H]+ permit distinction of the analyzed diastereomers, and enable evaluation of their relative content in a mixture with no need of chromatographic separation. The performed quantum chemical calculation have shown that protonated pseudoephedrine contains stronger hydrogen bond than protonated ephedrine, which can justify the observed higher relative abundance of ion [M+H–H2O]+ in the mass spectrum of pseudoephedrine, in comparison to that of ephedrine.

Erastin, a classical ferroptosis inducer, exerts cytotoxicity in several types of cancer cells including gastric cancer cells. However, the mechanism of erastin in regulating metabolic pathways in gastric cancer remains largely unclear. To investigate the gastric cellular response to erastin therapy, a pseudotargeted metabolomics method was achieved on ultra-high performance liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (UHPLC-QTRAP MS), which was used to investigate metabolic changes between erastin-treated MGC-803 cells and the controls at different time points. We found that erastin induced tremendous impact on the metabolome of gastric cells by affecting key metabolic processes, such as cysteine and methionine metabolism, tryptophan metabolism, purine metabolism, glutathione biosynthesis, glycolysis and TCA cycle. Interestingly, S-adenosylmethionine, methionine, serine and cysteine were obviously increasing treads after erastin treatment, while S-adenosylhomocysteine and glutathione were always down-regulated up to 24 h. The results indicated that DNA methylation was activated and glutathione biosynthesis was blocked in erastin-treated MGC-803 gastric cells, highlighting the importance of erastin as a promising drug candidate for in vivo treatment of gastric tumor.

Nitrate adducts of nitroglycerin (NG) and 1,3-dinitroglycerin (1,3-DNG) were produced from atmospheric pressure chemical ionization with chloride reagent ions and in-source decomposition of M·Cl−. The nitrate adducts subsequently dissociated in the drift region with enthalpies of 109 ± 9 kJ mol −1 at 142–150 °C for NG·NO3− and 101 ± 8 kJ mol−1 at 161–173 °C for 1,3-DNG·NO3−. Similar behavior was not observed generally for other explosives although nitrate adducts of each explosive could be formed using electrospray ionization with a nitrate salt solution. Ion abundances were measured over a range of ion energies with collision induced dissociation in tandem mass spectrometry and models from Density Functional Theory were used to correlate the experimental findings to structural motifs and other adduct properties. The computational modeling showed that adduct stability is dominated by the electrostatic interaction between the nitrate ion and the dipole moment of the neutral explosive. Specifically, explosives having the ability to adapt a conformer with a large dipole moment showed the most stable adducts. Other binding contributions are possible yet were found to be minor in the explosive adducts studied here.

The fragmentation behavior of some selected synthetic (1,2-diphytanyl- and 1,2-dihexadecyl-glycerophosphatidylethanolamine, 1,2-diphytanyl- and 1,2-dihexadecyl-glycerophosphatidylcholine) as well as of one natural diether phospholipid (2,3-diphytanyl-glycerophosphatidylinositol), the latter obtained from extracts of the archaeon Sulfolobus acidocaldaricus, was described by negative- and positive-ion MALDI high-energy CID tandem time-flight mass spectrometry for the first time. In contrast to the fragmentation pathways of classical diester glycerophospholipids, whose fragmentation behavior is already well described, the investigated diether glycerophospholipids exhibited a very different fragmentation behavior. The [M–H]−-precursor ions (ethanolamine, inositol) showed abundant high-mass charge-remote site fragmentation of the alkyl chains with easy determination of all methyl branching points (if present). Corresponding low mass product ions elucidated the identity of the polar head group. In contrast, [M+H]+-precursor ions of ethanolamine derivatives showed unusual loss of H3PO4 directly from the precursor ion and McLafferty-like rearrangements of selected product ions differing between sn1-and sn2-substituents, [R1O+58]+ and [R2O+42]+ ions, respectively. No diagnostic low mass product ions or high mass charge-remote site fragmentations are observed. A yet undescribed rearrangement reaction for protonated diether phosphocholine derivates was found by an intramolecular transesterification rearrangement of the precursor ion forming protonated O-alkyl glycerophosphatidylcholine. Besides, high mass charge-remote site fragmentation of the alkyl chains was observed. High-energy CID-spectra of [M+Na]+-precursor ions showed only little fragmentation (ethanolamine, inositol) with abundant partial polar head group losses and low mass head group product ions. In contrast, the [M+Na]+-precursor ions of corresponding choline derivatives showed significant charge-remote site fragmentation of the alkyl chains and diagnostic low mass head group ions. In case of the ethanolamine derivatives the [M+2Na–H]+-precursor ions exhibited abundant polar head group losses and high mass charge-remote site fragmentation with diagnostic low mass head group product ions. The inositol derivative mainly yielded disodiated dehydrated inositol phosphate as product ions. Finally, two diether phospholipid-specific product ions, the newly described K- and L-type ions, are described for the first time for all lipid derivatives and their mechanism of formation is described in detail.

Sesquiterpene pyridine alkaloids (SPAs) are a large group of macrocyclic dilactones formed by dihydro-β-agarofuran sesquiterpenes and pyridine dicarboxylic acids, which have aroused widespread interest in the field of medicine due to their significant biological activities. In order to achieve accurate and rapid characterization of SPAs, previous studies have systematically investigated their fragmentation patterns in MS2, but there are still some problems that need to be resolved, such as distinction between wilfordate (W)- and evoninate (E)-subtypes, as well as determination of the substituent position. In this paper, a comparative analysis of W- and E-subtypes of SPAs was carried out by a product ion scanning-multistage fragmentation (PIS-MSn) strategy using ultra-high-performance liquid chromatography/linear ion trap quadrupole/orbitrap mass spectrometry (UHPLC/LTQ-Orbitrap-MS). The precursor ions for MSn were selected from the ions related with pyridine dicarboxylic acid moiety in MS2 spectrum, such as the ions at m/z 206, 178, and 160. The results showed that the product ions at m/z 104 or 117 were produced in the MS4 spectra of W-subtype SPAs ([M+H]+ > m/z 160 > m/z 132 > m/z 104 or 117). The ion at m/z 104 was produced when acetyloxyl group was present at C-5, whereas the ion at m/z 117 was produced when hydeoxyl group was present at C-5. Neither of the above characteristic ions were produced in the MS4 spectra of E-subtype SPAs. The fragmentation mechanism was also deduced. In addition, 13 SPAs were identified from the root of Tripterygium wilfordii, including 1 unknown compound using the MS/MS fragmentation pattern. The findings in this study enable the differentiation between W- and E-subtypes of SPAs and, to a certain extent, solve the problem of substituent position, which is of great significance for the accurate and in-depth identification of SPAs.

Based on the laser resonance ionization mass spectrometry (LRIMS) developed in the laboratory, a preliminary method was established to determine Pu isotope ratios. A three-color-three-photon resonance ionization scheme was confirmed, and the laser wavelengths of each excitation/ionization step were λ1 = 586.654 nm, λ2 = 606.181 nm and λ3 = 642.722 nm. The selective ionization of 238Pu/238U was realized by testing the Pu and U mixed sample, a selectivity ratio of over 107 was obtained. More effective electrothermal atomization of Pu was implemented by loading graphene oxide solution on the Pu sample surface, and the total detection efficiency of ∼40 ng Pu sample was above 3 × 10−4, which was three orders of magnitude higher than the efficiency of the unloaded graphene oxide solution Pu sample. Results showed that the relative standard deviation of 238Pu/239Pu ratio was ∼0.20%, indicating that LRIMS could effectively avoid the isobaric interference of 238U faced by other commercial mass spectrometers such as TIMS and ICP-MS, and could achieve precise measurement of 238Pu/239Pu ratio.

Electrospray ionization plays a central role in modern analytical chemistry. It is often used in combination with an HPLC system and is able to transfer large molecules, such as proteins and complexes, into the gas phase. A liquid solution containing the analyte is sprayed in a strong electric field. Charged droplets generated by this process release the analyte molecules which can ultimately be analyzed by the mass spectrometer system. However, the exact mechanisms of droplet generation and ion release are still not fully understood and are under investigation. Recent literature puts the focus on droplet disintegration and shows that the analyte ions are not exclusively released from the droplets within the ionization chamber but rather in the whole mass spectrometer system. Previous experiments allow the direct observation of the signatures of fragmented droplets within the analyzer region of a time-of-flight mass spectrometer: An oscilloscope was connected to a secondary electron multiplier which serves as an auxiliary ion detector, located downstream of the orthogonal acceleration stage of a time-of-flight mass spectrometer. The oscilloscope is thus able to monitor the time-resolved ion current in the mass analyzer region. Pulses of extraordinarily high ion currents are observable here which are attributed to aspirated charged droplets.This work provides insights into long-term experiments with this experimental setup. There is a focus on signal stability, in the presence of such droplet signatures. It is apparent that the standby time of the instrument between individual measurements and the time since a switch of the polarity mode, has a significant influence on the signal stability. There are also indications that the observations of droplet signatures and the MS signal stability are correlated.

Capillary vibrating sharp-edge spray ionization (cVSSI) combined with hydrogen/deuterium exchange-mass spectrometry (HDX-MS) has been utilized to characterize different solution-phase DNA conformers including DNA G-quadruplex topologies as well as triplex DNA and duplex DNA. In general, G-quadruplex DNA shows a wide range of protection of hydrogens extending from ∼12% to ∼21% deuterium incorporation. Additionally, the DNA sequences selected to represent parallel, antiparallel, and hybrid G-quadruplex topologies exhibit slight differences in deuterium uptake levels which appear to loosely relate to overall conformer stability. Notably, the exchange level for one of the hybrid sequence sub topologies of G-quadruplex DNA (24 TTG) is significantly different (compared with the others studied here) despite the DNA sequences being highly comparable. For the quadruplex-forming sequences, correlation analysis suggests protection of base hydrogens involved in tetrad hydrogen bonding. For duplex DNA ∼19% deuterium incorporation is observed while only ∼16% is observed for triplex DNA. This increased protection of hydrogens may be due to the added backbone scaffolding and Hoogsteen base pairing of the latter species. These experiments lay the groundwork for future studies aimed at determining the structural source of this protection as well as the applicability of the approach for ascertaining different oligonucleotide folds, co-existing conformations, and/or overall conformer flexibility.

Overall, the nanoflow chromatographic separation, nano-electrospray source, and Orbitrap Elite mass spectrometer with the dual-stage ion funnel that replaced the standard heated-cone inlet were used in the MS analysis of low-abundance peptide samples. The analytical advantage of the ion funnel was demonstrated in the LC-MS analysis of HeLa protein digest mixture. Chemical noise patterns in Orbitrap, linear ion traps, and quadrupole time-of-flight mass spectrometers were compared. The chemical noise patterns in Orbitrap were found to be generally similar to those observed in linear ion traps and time-of-flight instruments, yet under conditions of selecting a limited mass range for the mass analysis. Ultrahigh mass resolution attained in Orbitrap allowed revealing internal structure in the chemical noise patterns. In addition to singly charged ions representing a bulk of chemical noise, the doubly charged ions were also observed, though the intensity of the latter was found to be significantly lower, suggesting that chemical noise-limited detection levels in low-abundance peptide MS analysis could be significantly lower for 2+ or 3+ peptide ions compared to singly charged ones.