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The spread of COVID-19 outbreak in 2020 had significant impact on the functioning of the existing healthcare system and required fast adaption to new circumstances for continuing with daily practices. Community pharmacists shared responsibility of ensuring supply of medicines and medical devices, educating people on health related issues, providing pharmaceutical care etc. The aim of this study was to understand how the provision of community pharmacy services changed during the first wave of COVID-19 pandemic in spring of 2020 in Estonia. Qualitative in-depth semi-structured interviews were conducted. Recorded interviews with community pharmacists (n = 21) and experts (n =10) were transcribed verbatim and a systematic text condensation method for textual content analysis was performed. The findings indicated that a number of changes took place in provision of community pharmacy services to assure continuity in providing high-quality pharmacy services in crisis, including addressing difficulties in the supply of medicines; at the same time, to acquire new knowledge for counselling health related topics and personal protective equipment, and to provide psychological support to people in stress. Pandemic had an impact on the content and structure of traditional community pharmacy services in Estonia. The need for expanded professional role of pharmacists was clearly expressed in an emergency situation.

In Estonia, HMG-CoA reductase inhibitors are widely used to modify lipid levels but there are no current data on additional medicines prescribed alongside the statins. The aim of this study was to identify the frequency of potential clinically relevant interactions at a national level among an outpatient population treated with statins between January and June 2008, based on the prescription database of the Estonian Health Insurance Fund. This retrospective prevalence study included 203,646 outpatients aged 50 years or older, of whom 29,367 received statin therapy. The study analysed individuals who had used at least one prescription medicine for a minimum of 7 days concomitantly with statins. Potential drug interactions were analysed using Epocrates online, Stockley’s Drug Interactions, and the drug interaction database developed in Estonia. Statins metabolised by the CYP3A4 isoenzyme were prescribed to 64% of all statin users. Medicines known to have potentially clinically significant interactions with statins were prescribed to 4.6% of patients.

Hydrothermal fluid plays a crucial role in the generation and migration of hydrocarbons within sedimentary basins. Herein, we employed bulk analysis and high-resolution mass spectrometry techniques to investigate the transformation dynamics from source rock to hydrocarbons under conditions influenced by magmatic activities in the Kongdian Formation, Huanghua Depression, China. The results revealed that hydrocarbon generation in the Ek 2 shale of the study area was significantly influenced by abnormal heating from hydrothermal fluids. High temperatures associated with these fluids accelerated the conversion of organic matter within source rocks, enhancing hydrocarbon generation rates. Subsequently, the hydrocarbons migrated into fracture networks, where they solidified as low-reflectance solid bitumen, forming trapped fractures of pyrobitumen and authigenic mineral aggregates leached from thermal fluid. High aliphatic fractions were noted in the source rock extracts, while extracts from low-reflectance solid bitumen exhibited higher aromatic fraction. Aliphatic and aromatic compounds in extracts from both the low-reflectance solid bitumen and the source rock exhibited similar maturities and origins. Regarding polar compounds, the compound classes O 1 , O 2 , N 1 O 1 , and N 1 O 2 showed higher abundances in source rock extracts compared to those in low-reflectance solid bitumen, while the S 1 and N 1 classes showed the opposite trend. Thus, fractionation clearly occurs when hydrocarbons expelled from source rocks by thermal fluids solidify into low-reflectance solid bitumen. This unique study provides valuable insights into understanding the fate of hydrocarbons originating from source rocks heated by thermal fluids, and explores the potential for unconventional oil in regions with intense hydrothermal alteration.

Rationale: The development of analytical screening techniques for pesticides is crucial for preventing and mitigating environmental contamination. Mass spectrometry-based screening methods differ based on the complexity of the sample matrix and the diversity of the target compounds. One of the major challenges is balancing cost reduction in the extraction process with the optimization of analytical results. This protocol introduces a universal and efficient scheme for the qualitative and quantitative schemes for 45 pesticides within a single analytical run., Methods: Water samples were extracted using an SPE column, with the pH adjusted to 7. Soil samples were processed using a modified QuEChERS method. The pretreatment for water samples emphasized selecting appropriate SPE columns and optimizing pH, while for soil samples, the focus was on choosing suitable extraction solvents and extraction salt packages. The enriched samples were then analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was evaluated for accuracy, precision, detection limits, and matrix effects., Results: The method enabled the simultaneous detection of 45 pesticides within a 15-minute analysis period. SPE recoveries ranged from 56.1% to 118.8%. Instrumental detection limits varied between 0.02 and 1 pg, while method detection limits extended from 0.05 to 18.47 ng/l in soil and water matrices. The approach was successfully applied to water and soil samples, with the pesticide concentration ranging from 0.1 ng/L to 38 μg/L., Conclusions: The protocol substantially enhances the characterization and quantification of 45 pesticides in environmental samples, achieving a remarkable reduction in detection limits by an order of magnitude compared to previous research. This method enables the simultaneous detection of pesticides in both water and soil matrices using a single system, addressing the challenges of using separate systems for different environmental media. Furthermore, this protocol provides a crucial theoretical foundation for managing and safeguarding against pesticide pollution., (© 2024 John Wiley & Sons Ltd.)

The exchange and transformation of dissolved organic matter (DOM) at the sediment-water interface are crucial factors in regulating watershed biogeochemistry, with the molecular composition of DOM serving as a pivotal determinant in elucidating this process. High-resolution mass spectrometry (HRMS) is an effective tool for resolving the composition of DOM. By analyzing the compositional characteristics of DOM at the sediment-water interface under three different salinities at the same latitude region in northern China, the findings indicate certain variations in component characteristics of DOM between low-salinity inland waters and high-salinity seawaters, with the former exhibiting greater molecular diversity and higher molecular weights, whereas the latter displayed a higher saturation and bioavailability. Notably, the presence of more CHOS substances in the low-salinity inland waters underscores the transformation of the DOM influenced by terrestrial inputs and anthropogenic activities. Conversely, the presence of more CHO and CHNO substances in high-salinity seawater underscores the microbial effects. The chemical transformation process from overlying water to pore water to sediments was characterized by methylation, hydrogenation, decarboxylation, and reduction, as determined by calculating the relations between the H/C and O/C ratios of different compound types. These findings indicate that HRMS can yield more refined results in revealing the process of DOM at the sediment-water interface under different environments, which provides a more reliable basis for a deeper understanding of the source-sink mechanism of sediment organic matter.

We used electrospray ionization and ion mobility spectrometry-mass spectrometry to detect and characterize the three anticancer drugs palbociclib, copanlisib, and olaparib. Ion mobility-mass spectrometry and density functional theory revealed that these compounds generate isomers during ionization (protomers) due to the presence of multiple protonation sites within their chemical structures. Our work has implications for understanding the solution- and gas-phase chemistry of these molecules during spray-based ionization processes.

Rationale: The sources and chemical compositions of organic aerosol (OA) exert a significant influence on both regional and global atmospheric conditions, thereby having far-reaching implications on environmental chemistry. However, existing mass spectrometry (MS) methods have limitations in characterizing the detailed composition of OA due to selective ionization as well as fractionation during cold-water extraction and solid-phase extraction (SPE)., Methods: A comprehensive MS study was conducted using aerosol samples collected on dusty, clean, and polluted days. To supplement the data obtained from electrospray ionization (ESI), a strategy for analyzing OAs collected using the quartz fiber filter directly utilizing laser desorption ionization (LDI) was employed. Additionally, the ESI method was conducted to explore suitable approaches for determining various OA compositions from samples collected on dusty, clean, and polluted days., Results: In situ LDI has the advantages of significantly reducing the sample volume, simplifying sample preparation, and overcoming the problem of overestimating sulfur-containing compounds usually encountered in ESI. It is suitable for the characterization of highly unsaturated and hydrophobic aerosols, such as brown carbon-type compounds with low volatility and high stability, which is supplementary to ESI., Conclusions: Compared with other ionization methods, in situ LDI helps provide a complementary description of the molecular compositions of OAs, especially for analyzing OAs in polluted day samples. This method may contribute to a more comprehensive MS analysis of the elusive compositions and sources of OA in the atmosphere., (© 2024 John Wiley & Sons Ltd.)

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have raised urgent environmental issues. The dissolved organic matter (DOM) plays a pivotal role on PPCPs' migration and transformation. To obtain a comprehensive understanding of the occurrence and distribution of PPCPs, a seasonal sampling focused on the riverine system in coastal zone, Tianjin, Bohai Rim was conducted. The distribution and transformation of thirty-three PPCPs and their interaction with DOM were investigated, and their sources and ecological risks were further evaluated. The total concentration of PPCPs ranges from 0.01 to 197.20 μg/L, and such value is affected by regional temperature, DOM and land use types. PPCPs migration at soil-water interface is controlled by temperature, sunlight, water flow and DOM. PPCPs have a high affinity to the protein-like DOM, while the humus-like DOM plays a negative influence and facilitates PPCPs' degradation. It is also found that protein-like DOM can represent point source pollution, while humus-like substances indicate non-point source (NPS) emission. Specific PPCPs can be used as markers to trace the source of domestic discharge. Additionally, daily use PPCPs such as ketoprofen, caffeine and iopromide are estimated to be the main risk substances, and their ecological risk varies on space, season and river hydraulic condition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A large body of research shows an association between higher body weight and low vitamin D status, as assessed using serum 25-hydroxyvitamin D concentrations. Vitamin D can be metabolised in adipose tissue and has been reported to influence gene expression and modulate inflammation and adipose tissue metabolism in vitro. However, the exact metabolism of vitamin D in adipose tissue is currently unknown. White adipose tissue expresses the vitamin D receptor and hydroxylase enzymes, substantially involved in vitamin D metabolism and efficacy. The distribution and concentrations of the generated vitamin D compounds in adipose tissue, however, are largely unknown. Closing this knowledge gap could help to understand whether the different vitamin D compounds have specific health effects in the setting of adiposity. This review summarises the current evidence for a role of vitamin D in adipose tissue and discusses options to accurately measure vitamin D compounds in adipose tissue using liquid chromatography tandem mass spectrometry (LC/MS-MS).

Sample preparation of complex, natural mixtures such as lignin prior to mass spectrometry analysis, however minimal, is a critical step in ensuring accurate and interference-free results. Modern shotgun-MS techniques, where samples are directly injected into a high-resolution mass spectrometer (HRMS) with no prior separation, usually still require basic sample pretreatment such as filtration and appropriate solvents for full dissolution and compatibility with atmospheric pressure ionization interfaces. In this study, sample preparation protocols have been established for a unique sample set consisting of a wide variety of degraded lignin samples from numerous sources and treatment processes. The samples were analyzed via electrospray (ESI)-HRMS in negative and positive ionization modes. The resulting information-rich HRMS datasets were then transformed into the mass defect space with custom R scripts as well as the open-source Constellation software as an effective way to visualize changes between the samples due to the sample preparation and ionization conditions as well as a starting point for comprehensive characterization of these varied sample sets. Optimized conditions for the four investigated lignins are proposed for ESI-HRMS analysis for the first time, giving an excellent starting point for future studies seeking to better characterize and understand these complex mixtures., (© 2023. The Author(s).)

In this study, we report a one-pot double derivatization scheme, which used acetylation after a Diels-Alder reaction using 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) to improve separation efficiency and provide baseline separations of the five vitamin D metabolites 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), 24,25-dihydroxyvitamin D3 (24,25(OH) 2 D 3 ), 3β-25-hydroxyvitamin D 3 (3β-25(OH)D 3 ), 3α-25-hydroxyvitamin D 3 (3α-25(OH)D 3 ) and vitamin D 3 on a C-18 stationary phase. Vitamin D metabolites are often very challenging to measure quantitatively using mass spectrometry, due to their low serum concentration levels and low ionization efficiencies. Moreover, some of these species are isomers with virtually identical mass spectral dissociation behavior. To overcome the low ionization efficiency and unspecific fragmentation behavior, derivatization using Diels-Alder reactions with Cookson-type reagents such as PTAD are common. These derivatization reactions generally result in more complicated liquid chromatography separations, because both 6R- and 6S-isomers are formed during Diels-Alder reactions. It has been shown that separations have been particularly challenging for the 3α-25(OH)D 3 and 3β-25(OH)D 3 epimers. Here, we optimized the PTAD derivatization and the esterification using acetic anhydride. By utilizing the esterification catalyst 4-dimethylaminopyridine, we avoided quenching and evaporation between the two derivatization steps, but were also able to perform the esterification at room temperature without heating. The optimized one-pot double derivatization LC-MS/MS assay was validated with respect to inter/intra-day precision, accuracy, recovery and linear dynamic range and applied to metabolic fingerprinting of vitamin D 3 metabolites in serum samples. The metabolites 3α-25(OH)D 3 , 3β-25(OH)D 3 and 24,25(OH) 2 D 3 , were readily quantified in all investigated samples. The method was, in principle, also fit for purpose for quantification of the native vitamin D 3 species; the relatively high blank concentration of the commercial vitamin D-depleted serum used for calibration, however, limited the limits of quantification for this metabolite. The method provided insufficient limits of quantification for serum levels of 1,25(OH) 2 D 3 ., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Dietrich Volmer reports financial support was provided by Humboldt University of Berlin. Dietrich Volmer reports a relationship with John Wiley & Sons Inc that includes: board membership., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We report the detection of early-stage intermediates of spontaneous free-radical oxidation of organic pollutants such as aliphatic amino alcohols and diamines in charged aqueous microdroplets in the ambient atmosphere. We propose that the intrinsic formation of reactive oxygen species at the air-water interface is responsible for the radical oxidation of the sp3 carbon. We suggest that our work will aid the understanding of the degradation mechanisms of organic molecules in the environment.

Liquid chromatography/tandem mass spectrometry is firmly established today as the gold standard technique for analysis of vitamin D, both for vitamin D status assessments as well as for measuring complex and intricate vitamin D metabolic fingerprints. While the actual mass spectrometry technology has seen only incremental performance increases in recent years, there have been major, very impactful changes in the front- and back-end of MS-based vitamin D assays; for example, the extension to new types of biological sample matrices analyzed for an increasing number of different vitamin D metabolites, novel sample preparation techniques, new powerful chemical derivatization reagents, as well the continued integration of high resolution mass spectrometers into clinical laboratories, replacing established triple-quadrupole instruments. At the same time, the sustainability of mass spectrometry operation in the vitamin D field is now firmly established through proven analytical harmonization and standardization programs. The present review summarizes the most important of these recent developments., (© 2021 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd.)

Vitamin D analysis by MS faces several analytical challenges, including inefficient ionization, nonspecific fragmentation, interferences from epimers, isomers, and isobars, as well as very low concentration levels. In this study, we used 2-fluoro-1-methylpyridinium (FMP) p-toluene sulfonate for derivatization of vitamin D3 metabolites to increase detection sensitivity and allow for full chromatographic separation of vitamin D isomers and epimers. UHPLC-MS/MS was used for measurement of five vitamin D3 metabolites in human serum. Compared with Amplifex and 4-phenyl-1,2,4-triazolin-3,5-dion, the FMP p-toluene sulfonate reaction required less time to be performed. The method was optimized and validated to ensure accuracy, precision, and reliability. In-house and commercial quality control samples were used to assure the quality of the results for 25-hydroxyvitamin D3. The method showed very good linearity and intraday and interday accuracy and precision; coefficients of determination (r 2 ) ranged between 0.9977 and 0.9992, relative recovery from 95 to 111%, and coefficient of variation from 0.9 to 11.3. Stability tests showed that the extracted derivatized serum samples were stable for 24 h after storage at -20°C; 24,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D3-FMP derivatives were stable for 1 week at -80°C. The method was applied to samples of healthy individuals for quantitative determination of vitamin D3, the two epimers of 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The present study systematically compares the sensitivity and selectivity of the analysis of multiple vitamin D metabolites after chemical derivatization using different reagents for liquid chromatography-tandem mass spectrometry (LC-MS/MS). Generally, chemical derivatization is applied to vitamin D metabolites to increase the ionization efficiency, which is particularly important for very low abundant metabolites. Derivatization can also improve the selectivity of the LC separation. A wide variety of derivatization reagents has been reported in recent years, but information on their relative performance and applicability to different vitamin D metabolites is, unfortunately, not available in the literature. To fill this gap, we investigated vitamin D 3 , 3β-25-hydroxyvitamin D 3 (3β-25(OH)D 3 ), 3α-25-hydroxyvitamin D 3 (3α-25(OH)D 3 ), 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), and 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ) and compared response factors and selectivity after derivatizing with several important reagents, including four dienophile reagents (4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), 4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalinyl)ethyl]-1,2,4-triazoline-3,5-dione (DMEQ-TAD), Amplifex, 2-nitrosopyridine (PyrNO)) as well as two reagents targeting hydroxyl groups: isonicotinoyl chloride (INC) and 2-fluoro-1-methylpyridinium-p-toluenesulfonate (FMP-TS). In addition, a combination of dienophiles and hydroxyl group reagents was examined. For LC separations, reversed-phase C-18 and mixed-mode pentafluorophenyl HPLC columns using different compositions of the mobile phase were compared. With respect to detection sensitivity, the optimum derivatization reagent for the profiling of multiple metabolites was Amplifex. Nevertheless, FMP-TS, INC, PTAD, or PTAD combined with an acetylation reaction showed very good performance for selected metabolites. These reagent combinations provided signal enhancements on the order of 3- to 295-fold depending on the compound. Chromatographic separation of the dihydroxylated vitamin D 3 species was readily achieved using any of the derivatization reactions, while for 25(OH)D 3 epimers, only PyrNO, FMP, INC, and PTAD combined with acetylation enabled complete separation. In conclusion, we believe this study can serve as a useful reference for vitamin D laboratories, to help analytical and clinical scientists decide which derivatization reagent to choose for their application., (© 2023. The Author(s).)

The combination of acoustically levitated droplets, mid-IR laser evaporation, and subsequent post-ionization by secondary electrospray ionization was applied for monitoring the enzymatic digestion of various proteins. Acoustically levitated droplets are an ideal, wall-free model reactor, readily allowing compartmentalized microfluidic trypsin digestions. Time-resolved interrogation of the droplets yielded real-time information on the progress of the reaction and thus provided insights into reaction kinetics. After 30 min of digestion in the acoustic levitator, the obtained protein sequence coverages were identical to the reference overnight digestions. Importantly, our results clearly demonstrate that the applied experimental setup can be used for the real-time investigation of chemical reactions. Furthermore, the described methodology only uses a fraction of the typically applied amounts of solvent, analyte, and trypsin. Thus, the results exemplify the use of acoustic levitation as a green analytical chemistry alternative to the currently used batch reactions.

Sauce-flavor Baijiu is one of the most complex and typical types of traditional Chinese liquor, whose trace components have an important impact on its taste and quality. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is one of the most favorable analytical tools to reveal trace molecular components in complex samples. This study analyzed the chemical diversity of several representative sauce-flavor Baijiu using the combination of electrospray ionization (ESI) and FT-ICR MS. The results showed that ESI+ and ESI- exhibited different chemical features characteristic of trace components. Overall, sauce-flavor Baijiu was dominated by CHO class compounds, and the main specific compound types were aliphatic, highly unsaturated with low oxygen, and peptide-like compounds. The mass spectral parameters resolved by FT-ICR MS of several well-known brands were relatively similar, whereas the greatest variability was observed from an internally supplied brand. This study provides a new perspective on the mass spectrometry characteristics of trace components of sauce-flavor Baijiu and offers a theoretical foundation for further optimization of the gradients in Baijiu.

The field of high-resolution mass spectrometry (HRMS) and ancillary hyphenated techniques comprise a rapidly expanding and evolving area. As popularity of HRMS instruments grows, there is a concurrent need for tools and solutions to simplify and automate the processing of the large and complex datasets that result from these analyses. Constellation is one such of these tools, developed by our group over the last two years to perform unsupervised trend detection for repeating, polymeric units in HRMS data of complex mixtures such as natural organic matter, oil, or lignin. In this work, we develop two new unsupervised algorithms for finding chemically-meaningful changing units in HRMS data, and incorporate a molecular-formula-finding algorithm from the open-source CoreMS software package, both demonstrated here in the Constellation software environment. These algorithms are evaluated on a collection of open-source HRMS datasets containing polymeric analytes (PEG 400 and NIST standard reference material 1950, both metabolites in human plasma, as well as a swab extract containing polymers), and are able to successfully identify all known changing units in the data, including assigning the correct formulas. Through these new developments, we are excited to add to a growing body of open-source software specialized in extracting useful information from complex datasets without the high costs, technical knowledge, and processor-demand typically associated with such tools., (© 2023. The Author(s).)

Rationale: The development of appropriate analytical screening techniques for pharmaceuticals and personal care products (PPCPs) is the basis for studying the distribution and environmental impact of emerging contaminants (ECs). Mass spectrometry-based screening methods vary with the complexity of the target compounds. It is challenging to balance both positive and negative ion quantification with a low detection limit. To establish a set of experimental methods including extraction, chromatography-separation and mass spectrometry screening is one of the most important topics in PPCP research. This paper describes a universal and efficient qualification and quantification protocol for the simultaneous detection of 34 PPCPs in different environmental samples in a single analytical data acquisition run., Methods: Thirty-four representative PPCPs, which are widely distributed in the environment with high ecological toxicity and complex chemical structures, were selected as representative target ECs. The extraction of the target PPCPs was achieved using only one solid-phase extraction cartridge without the need to adjust the pH of samples. The enriched samples were detected by LC-MS/MS in both positive and negative ion modes simultaneously. The protocol was evaluated based on the accuracy, precision, detection limits and matrix effects., Results: This method achieved simultaneous detection of PPCPs in both positive and negative ion modes, with a single analytical cycle of 12 min. The observed SPE recoveries were between 40% and 115%. The instrumental detection limits (IDL) varied from 0.01 to 1 pg, and the method detection limits (MDL) were between 0.002 and 3.323 ng/l in different matrices. Most of the PPCPs were subjected to matrix suppression below 30%. The method was successfully applied for quantitative analysis of the PPCPs in different environmental samples, including river samples, wastewater treatment plant (WWTP) samples and soil samples., Conclusions: This protocol developed a rapid and efficient detection method to simultaneous qualitative and quantitative 34 representative PPCPs in the environment. The IDL ranged from 0.01 to 1 pg and the MDL ranged from 0.002 to 3.323 ng/l in different matrices. The detection limit was one order of magnitude lower compared to previous studies. The protocol also provided a wide application range for different environmental matrices, which permitted the migration and transformation of PPCPs to be explored., (© 2022 John Wiley & Sons Ltd.)

Lignin is currently one of the most promising biologically derived resources, due to its abundance and application in biofuels, materials and conversion to value aromatic chemicals. The need to better characterize and understand this complex biopolymer has led to the development of many different analytical approaches, several of which involve mass spectrometry and subsequent data analysis. This review surveys the most important analytical methods for lignin involving mass spectrometry, first looking at methods involving gas chromatography, liquid chromatography and then continuing with more contemporary methods such as matrix assisted laser desorption ionization and time-of-flight-secondary ion mass spectrometry. Following that will be techniques that directly ionize lignin mixtures-without chromatographic separation-using softer atmospheric ionization techniques that leave the lignin oligomers intact. Finally, ultra-high resolution mass analyzers such as FT-ICR have enabled lignin analysis without major sample preparation and chromatography steps. Concurrent with an increase in the resolution of mass spectrometers, there have been a wealth of complementary data analyses and visualization methods that have allowed researchers to probe deeper into the "lignome" than ever before. These approaches extract trends such as compound series and even important analytical information about lignin substructures without performing lignin degradation either chemically or during MS analysis. These innovative methods are paving the way for a more comprehensive understanding of this important biopolymer, as we seek more sustainable solutions for our human species' energy and materials needs., (© 2021 The Authors. Mass Spectrometry Reviews Published by John Wiley & Sons Ltd.)

Liquid chromatography/tandem mass spectrometry (LC-MS/MS) is widely used to determine vitamin D 3 metabolites in biological samples. The ionization efficiencies of these metabolites, however, are poor under electrospray ionization conditions. Moreover, the chromatographic separation of multiple vitamin D metabolites and their epimers can be challenging. For these reasons, chemical derivatization reagents are often used to improve sensitivity and selectivity of analysis. While the derivatization schemes have been proven to be very effective, one missing aspect is the investigation of the stability of the chemical derivatization products in stored sample extracts. In this study, we investigated the long-term stability of several vitamin D 3 metabolites after 1 and 3 months of storage at - 20 °C. Five vitamin D 3 metabolites were examined after derivatization with seven different derivatization reagents. Generally, Amplifex products were the most stable in the long term in our study with 11-20% degraded after 1 month of storage and 14-35% after 3 months. The stabilities for some of the metabolites' 4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalyl)ethyl]-1,2,4-triazoline-3,5-dione (DMEQ-TAD), 2-fluoro-1-methylpyridinium p-toluenesulfonate (FMP-TS), isonicotinoyl chloride (INC) and 4-phenyl-1,2,4-triazoline-3,5-dione acetylated (PTAD-Ac) products were also acceptable after 1 month of storage. Other derivatized metabolites, however, degraded extensively already after 1 month of storage, such as 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) (54-72% degradation) and 2-nitrosopyridine (PyrNO) (32-100% degradation). Importantly, for every metabolite, there was an optimum derivatization reagent that met the criteria of stability proposed by international regulatory bodies after 1 month of storage. Some derivatives were stable for even up to 3 months of storage, with degradation of less than 15%., (© 2022. The Author(s).)

The composition of acoustically levitated droplets was probed by a novel combination of mid-IR laser evaporation and subsequent postionization via secondary electrospray ionization. The combination of microliter samples and subnanoliter sampling provided time-resolved interrogation of droplets and allowed for a kinetic investigation of the laser-induced release of the analyte, which was found to strongly depend on the analytes. The observed substance-specific delayed release of the analytes permitted baseline-separated discrimination of the analytes, ideal for the study of complex samples. The additionally applied postionization scheme was found to enable efficient detection of small volatile compounds as well as peptides. The detection of small molecules and peptides occurred under very different sampling geometries, pointing to two distinct underlying ionization mechanisms. Overall, our results suggest that the experimental setup presented in this study can serve as a widely applicable platform to study chemical reactions in acoustically levitated droplets as model reactors.

Rationale: Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) combined with different ionization techniques provides a powerful means to characterize dissolved organic matter (DOM) at the molecular level. Solid-phase extraction (SPE) is currently the most widely utilized method for extracting the DOM, but one-step elution using methanol does not provide a comprehensive picture of DOM. The development of efficient extraction and enrichment methods as well as characterization techniques from water samples remains a priority for DOM research, which is investigated in this study., Methods: The DOM was extracted from lake water by SPE using one-step elution (methanol or dichloromethane) and multistep elution (water, methanol, acetone, and dichloromethane). A combination of electrospray ionization (ESI), atmospheric pressure photoionization (APPI), and matrix-free laser desorption ionization (LDI) was utilized for FT-ICR MS analysis in both positive (+) and negative (-) ion modes., Results: The total recovery of the multistep elution was 23.5% higher as compared to the investigated one-step elution procedure (85% vs. 61.6%); however, a comparison of the observed molecular species and the range of diversity under different ionization techniques along with the statistical analyses showed that proper selection of solvent and ionization method was required to explore specific compounds from the sample., Conclusions: For DOM species containing different heteroatoms, a combination of ESI, APPI, and LDI can offer a comprehensive profile of DOM in aquatic ecosystems. The specific molecular formulae of each ionization technique are characterized as follows: ESI- mode exhibited strong selectivity for lignin-like and tannins-like species with high oxygen content, as well as organosulfates. ESI+ favored lipid species and peptide/protein compounds. Unsaturated and condensed aromatic hydrocarbons with low oxygen were preferably ionized by both APPI and LDI., (© 2022 John Wiley & Sons Ltd.)

The sources and composition of dissolved organic matter (DOM) in rivers are critical to water quality and aquatic ecosystems. Studies on detailed composition of organic matter in rivers in the farming-pastoral ecotone are relatively limited in the research community. To better understand the characteristics and dynamics of DOM, Yang River in North China was selected as the study area because of its profound influences on the farming-pastoral ecotone nearby. A combination of fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) techniques revealed that the DOM composition of Yang River is driven by land use. DOM in Yang River is predominantly imported from allochthonous inputs, together with agricultural runoff, pastureland, and urban sewage, causing a comprehensive impact on DOM. In detail, DOM associated with cropland inputs was dominated by lignin-like species, with higher nitrogen content. In comparison, DOM related to grassland is more diverse and susceptible to degradation. An increase in urban areas led to an increase in sulfur-containing compounds, while their oxygen, nitrogen, and aromaticity contents were significantly lower than those in cropland. Interestingly, urban-influenced lignin-like compounds may be associated with the effluents from the pulp and paper mill. Additionally, synthetic surfactants from the lower section of the river were also structurally identified by tandem mass spectrometry. Overall, this study could provide valuable insights into the DOM sources and their transformation dynamics at a molecular level, which could be an indicator for riverine water quality management and be applied to other farming-pastoral ecotones straightforward., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Among the different techniques for mass analysis, ultra-high-resolution Fourier transform ion cyclotron resonance (FTICR) is the method of choice for highly complex samples, as it offers unrivaled mass accuracy and resolving power, combined with a high degree of flexibility in hybrid instruments as well as for ion activation techniques. FTICR instruments are readily embraced by the biological and biomedical research communities and applied over a wide range of applications for the analysis of biomolecules such as carbohydrates, lipids, nucleic acids, and proteins. In the field of natural organic matter (NOM) analysis, petroleum-related studies currently dominate FTICR-MS applications. Recently, however, there is a growing interest in developing high-performance MS methods for the characterization of NOM samples from natural aquatic and terrestrial environments. Here, we present an overview of FTICR-MS techniques for complex, non-petroleum NOM samples, including data analysis and novel tandem mass spectrometry (MS/MS) methods for structural classifications. © 2020 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd., (© 2020 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd.)

The determination of vitamin D metabolites as status marker or for diagnostic purposes is almost entirely conducted from blood serum or plasma. Other biological matrices, however, have also interested researchers, for two main reasons: (1) alternative matrices may allow non-invasive sampling, permit easier sample transfer and require less demanding storage conditions; and (2) the levels of vitamin D metabolites in other body compartments may further aid the understanding of vitamin D metabolism and function. Thus, the development of reliable and efficient sample preparation protocols for sample matrices other than serum/plasma, which will remove potential interferences and selectively extract the targeted metabolites, is of great importance. This review summarizes sample preparation methods for measurement of vitamin D metabolites using liquid chromatography-(tandem)mass spectrometry in more than ten different human tissues, including hair, saliva, adipose tissue, brain and others., (© 2022. The Author(s).)

Vitamin D compounds are a group of secosteroids derived from cholesterol that are vital for maintaining bone health in humans. Recent studies have shown extraskeletal effects of vitamin D, involving vitamin D metabolites such as the dihydroxylated vitamin D 3 compounds 1,25-dihydroxyvitamin D 3 and 24,25-dihydroxyvitamin D 3 . Differentiation and characterization of these isomers by mass spectrometry can be challenging due to the zero-mass difference and minor structural differences between them. The isomers usually require separation by liquid chromatography (LC) prior to mass spectrometry, which adds extra complexity to the analysis. Herein, we investigated and revisited the use of fragmentation methods such as collisional induced dissociation (CID), infrared multiphoton dissociation (IRMPD), electron induced dissociation (EID), and ultraviolet photodissociation (UVPD), available on a 12T Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) to generate characteristic fragments for the dihydroxylated vitamin D 3 isomers that can be used to distinguish between them. Isomer-specific fragments were observed for the 1,25-dihydroxyvitamin D 3 , which were clearly absent in the 24,25-dihydroxyvitamin D 3 MS/MS spectra using all fragmentation methods mentioned above. The fragments generated due to cleavage of the C-6/C-7 bond in the 1,25-dihydroxyvitamin D 3 compound demonstrate that the fragile OH groups were retained during fragmentation, thus enabling differentiation between the two dihydroxylated vitamin D 3 isomers without the need for prior chromatographic separation or derivatization.

The increasing popularity of high-resolution mass spectrometry has led to many custom software solutions to process, interpret, and reveal information from high-resolution mass spectra. Although there are numerous software packages for peak-picking, calibration, and formula-finding, there are additional layers of information available when it comes to detecting repeated motifs from polymers or molecules with repeating structures or products of chemical or biochemical transformations that exhibit systematic, serial chemical changes of mass. Constellation is an open-source, Python-based web application that allows the user first to expand their high-resolution mass data into the mass defect space, after which a trend finding algorithm is used for supervised or unsupervised detection of repeating motifs. Many adjustable parameters allow the user to tailor their trend-search to target particular chemical moieties or repeating units, or search for all potential motifs within certain limits. The algorithm has a built-in optimization routine to provide a good starting point for the main trend finding parameters before user customization. Visualization tools allow interrogation of the data and any trends/patterns to a highly specific degree and save publication-quality images directly from the interface. As Constellation is deployed as a web application, it is easily used by anyone with a web browser; no software download or high-powered computer is required, as computations are performed on a remote high-powered data server run by our group.

This tutorial review focuses on analytical challenges encountered with the liquid chromatography-tandem mass spectrometry determination of 25-hydroxyvitamin D, which is currently still considered the metabolite that is most representative of vitamin D status. It describes how multiple binding states of circulating 25-hydroxyvitamin D (phase II metabolites, epimers, free/bioavailable/protein-bound species) can influence the accuracy of the analytical determination. It also summarizes important chemical species that can inadvertently contribute to vitamin D status and thus cause systematic errors. These interfering endogenous and exogenous compounds might be isomers of vitamin D, constitutional isomers or isobars and the article outlines techniques to eliminate or minimize these interferences, including chromatographic separations, ion mobility spectrometry, and high-resolution mass spectrometry., Competing Interests: The authors declare no competing financial and nonfinancial interests. DAV is Editor‐in‐Chief of Analytical Science Advances., (© 2021 The Authors. Analytical Science Advances published by Wiley‐VCH GmbH.)

Objectives: This in situ study aimed to determine and compare the chlorhexidine (CHX) retention in the oral cavity after the application of different CHX pharmaceutical regimens., Methods: Five volunteers used different CHX treatment regimens including mouth rinses, dental spray and toothpaste gel. After the application of the different CHX regimens, 2-μl samples were taken from saliva and buccal mucosa pellicle as well as the dental pellicle samples formed on standardized enamel surfaces. Sample collection was conducted at six time points within 12 h. Retention of CHX was measured using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry., Results: CHX retention values in the oral mucosa pellicle were significantly higher than those in saliva. CHX remained in the mucosal pellicle at microgrammes per millilitre levels for 12 h after mouth rinsing, 10 h after spray application and 2 h after using the toothpaste. CHX was detected in the dental pellicle for at least 12 h after application of mouth rinsing and spray. Retention of CHX after mouth rinsing or spray application was significantly higher than the retention after using toothpaste., Conclusions: Oral mucosa was the favourable site for CHX retention. Higher mouth rinse concentration and longer rinsing time produced a slight increase in CHX retention. CHX spray provided considerable retention values, whereas toothpaste gel delivered the lowest retention after application. MALDI-TOF was a sensitive method with excellent limits of quantification for CHX detection., (© 2021. The Author(s).)

A combination of acoustic levitation, laser vaporization, and atmospheric pressure chemical ionization mass spectrometry (APCI-MS) is presented in this study that enabled sensitive analysis of pharmaceutical drugs from an aqueous sample matrix. An unfocused pulsed infrared laser provided contactless sample desorption from the droplets trapped inside an acoustic levitator by activation of the OH stretching band of aqueous and alcoholic solvents. Subsequent atmospheric pressure chemical ionization was used between the levitated droplet and the mass spectrometer for postionization. In this setup, the unfocused laser gently desorbed the analytes by applying very mild repulsive forces. Detailed plume formation studies by temporally resolved schlieren experiments were used to characterize the liquid gas transition in this process. In addition, the role of different additives and solvent composition was examined during the ionization process. The analytical application of the technique and the proof-of-concept for quantitative analysis were demonstrated by the determination of selected pharmaceutical drugs in aqueous matrix with limits of quantification at the lower nanomolar level and a linear dynamic range of 3-4 orders of magnitude.

The metabolism of vitamin D 3 includes a parallel C-3 epimerization pathway-in addition to the standard metabolic processes for vitamin D 3 -reversing the stereochemical configuration of the -OH group at carbon-3 (β→α). While the biological function of the 3α epimer has not been elucidated yet, the additional species cannot be neglected in the analytical determination of vitamin D 3 , as it has the potential to introduce analytical errors if not properly accounted for. Recently, some inconsistent mass spectral behavior was seen for the 25-hydroxyvitamin D 3 (25(OH)D 3 ) epimers during quantification using electrospray LC-MS/MS. The present work extends that of Flynn et al. ( Ann. Clin. Biochem. 2014, 51, 352-559) and van den Ouweland et al. ( J. Chromatogr. B 2014, 967, 195-202), who reported larger electrospray ionization response factors for the 3α epimer of 25(OH)D 3 in human serum samples as compared to the regular 3β variant. The present work was concerned with the mechanistic reasons for these differences. We used a combination of electrospray ionization, atmospheric pressure chemical ionization, and density functional theory calculations to uncover structural dissimilarities between the epimers. A plausible mechanism is described based on intramolecular hydrogen bonding in the gas phase, which creates a small difference of proton affinities between the epimers. More importantly, this mechanism allows the explanation of the different ionization efficiencies of the epimers based on kinetic control of the ionization process, where ionization initially takes place at the hydroxyl group with subsequent proton transfer to a basic carbon atom. The barrier for this transfer differs between the epimers and is in direct competition with H 2 O elimination from the protonated hydroxyl group. The "hidden" site of high gas phase basicity was revealed through computational calculations and appears to be inaccessible via direct protonation.

Lignin is the second most abundant natural biopolymer, which is a potential alternative to conventional fossil fuels. It is also a promising material for the recovery of valuable chemicals such as aromatic compounds as well as an important biomarker for terrestrial organic matter. Lignin is currently produced in large quantities as a by-product of chemical pulping and cellulosic ethanol processes. Consequently, analytical methods are required to assess the content of valuable chemicals contained in these complex lignin wastes. This review is devoted to the application of mass spectrometry, including data analysis strategies, for the elemental and structural elucidation of lignin products. We describe and critically evaluate how these methods have contributed to progress and trends in the utilization of lignin in chemical synthesis, materials, energy, and geochemistry.

Mass resolving power is one of the key features of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), which enables the molecular characterization of complex mixtures. Quadrupole (2ω) detection provides a significant step forward in FT-ICR MS performance, as it doubles the resolving power for a given signal acquisition time. Whether this 2ω detection technique truly substitutes for a higher magnetic field remains unknown however. In this study, a residue oil sample was characterized using both a 2ω 7 Tesla FT-ICR and a 15 Tesla FT-ICR instrument, and analytical figures of merit were systematically compared. It was shown that 2ω 7T FT-ICR MS provided comparable performance in the deep profiling of the complex oil sample, with better signal intensities and reproducibilities for absorption-mode processing. The 15T FT-ICR MS gave more precise measurements with better estimates of the sample's elemental compositions. To the best of our knowledge, this is the first published study, which thoroughly compared the performance of 2ω detection on a low magnetic field instrument with that of a high magnetic field FT-ICR-MS., Competing Interests: The authors declare no competing financial and nonfinancial interests. D.A.V. is Editor‐in‐Chief of Analytical Science Advances., (© 2020 The Authors. Analytical Science Advances published by Wiley‐VCH GmbH.)

Lignin is a highly complex, plant-derived natural biomass component, the analysis of which requires significant demands on the analytical platform. Fourier transform ion cyclotron mass spectrometry (FT-ICR MS) has been shown to be able to readily assess the complexity of lignin and lignin degradation products by assigning tens of thousands of compounds with elemental formulae. Nevertheless, many experimental and instrumental parameters introduce discrimination towards certain components, which limits the comprehensive MS analysis. As a result, a complete characterization of the lignome remains a challenge. The present study investigated a degraded lignin sample using FT-ICR MS and compared several atmospheric pressure ionization methods, e.g., electrospray ionization, atmospheric-pressure chemical ionization, and atmospheric-pressure photoionization. The results clearly show that the number of heteroatoms (e.g., N, S, P) in the sample greatly increases the chemical diversity of lignin, while at the same time also providing potentially useful biomarkers. We demonstrate here that FT-ICR MS was able to directly isolate isotopically pure single components from the ultra-complex mixture for subsequent structural analysis, without the time-consuming chromatographic separation. CAPSULE: Various ionization techniques coupled to FT-ICR MS provide a powerful tool to assess the lignome coverage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to determine chlorhexidine retention in different oral sites after a one-time 30 s mouth rinsing., Design: Five volunteers were asked to rinse their mouth with 10 ml of 0.2 % chlorhexidine digluconate for 30 s. After rinsing, samples were collected from the interdental area, buccal dental pellicle, anterior labial and posterior buccal mucosa, and saliva with a microbrush at five-time points within 24 h. Retention of chlorhexidine was measured using matrix-assisted laser desorption/ionization-time of flight mass spectrometry with a quantification limit of 15 ng/ml., Results: Chlorhexidine remained in the oral cavity at micrograms per milliliter levels for 11 h after mouth rinsing and was even detected 24 h after application. The results showed a distinct decline of intraoral chlorhexidine levels during the first 6 h after rinsing and it was then retained at low concentrations for at least 24 h., Conclusions: The dental pellicle and oral mucosa were favorable sites for chlorhexidine retention. The novel method used for chlorhexidine determination offered excellent quantification limits and readily permitted quantification of chlorhexidine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A series of ultrathin, homogenous gold nanoparticle (AuNP) substrates for surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) were prepared using a simple air/water interface approach. These SALDI substrates enabled soft ionization and provided significant improvements in terms of signal intensities and reduced background levels in comparison to other AuNP morphologies for different analytes such as fatty acids, peptides, amino acids, saccharides, and drugs. Through different microscopic and spectroscopic methods, we determined that the packing homogeneity of the [AuNP] n substrates played a vital role in the efficiency of the SALDI process. We demonstrated that the signal intensities of the investigated analytes were readily optimized by manipulating the thickness of the [AuNP] n substrates. The desorption/ionization efficiency increased as a function of the number of layers and then reached a saturation point. The optimized [AuNP] n substrates not only exhibited high SALDI-MS desorption/ionization efficiencies but also showed excellent reproducibilities of the analyte signals.

Overcoming the detrimental effects of sweet spots during crystallization is an important step to improve the quantitative abilities of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. In this study, we introduce MALDI targets, which exhibit a channel design to reduce sweet spot phenomena and improve reproducibility. The size of the channels was 3.0 mm in length, 0.35 mm in depth, and 0.40 mm in width, adjusted to the width of the implemented laser beam. For sample deposition, the matrix/sample mixture was homogenously deposited into the channels using capillary action. To demonstrate the proof-of-principle, the novel plates were used for the quantification of acetyl-L-carnitine in human blood plasma using a combined standard addition and isotope dilution method. The results showed that the reproducibility of acetyl-L-carnitine detection was highly improved over a conventional MALDI-MS assay, with RSD values of less than 5.9% in comparison with 15.6% using the regular MALDI method. The limits of quantification using the new plates were lowered approximately two-fold in comparison with a standard rastering approach on a smooth stainless-steel plate. Matrix effects were also assessed and shown to be negligible. The new assay was subsequently applied to the quantification of acetyl-L-carnitine in human plasma samples., (© 2019 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons Ltd.)

Lignin is the most abundant natural resource of aromatic moieties and the second most abundant natural biopolymer. Analytical techniques that obtain as much information as possible on the exact structural content of lignin species are essential for developing efficient processes that transform highly complex lignin wastes into value chemicals and biofuels. For mass spectrometric analysis of lignin samples, usually electrospray ionization, atmospheric pressure chemical ionization, or atmospheric pressure photoionization are used as ionization techniques. Matrix-assisted laser desorption/ionization (MALDI) is less frequently applied but offers a much more rapid screening option for lignin mixtures. In this study, we compared several common MALDI matrices for analysis of alkali lignin and discovered that different chemical matrices exhibited very different ionization efficiencies and selectivity with respect to the structures of the lignin-related compounds as well as the presence of heteroatoms. Importantly, the results highlight that the choice of matrix strongly determines the analytical coverage of molecular species in the complex lignin degradation mixtures. Graphical abstract.

Gas phase ion/molecule reactions are often used in analytical applications to support the analysis of isomers or to identify specific functional groups of organic molecules. Until now, deliberate chemical reactions have not been performed in differential ion mobility spectrometry (DMS) devices except for hydrogen exchange and cluster formation. The present work extends that of Colorado and Brodbelt (Anal Chem 66:2330-5, 1994) on ion/molecule reactions in an ion trap mass spectrometer. In this study, class-specific chemical reactions of 4-quinolone antibiotics with various chemical reagents were used to demonstrate the analytical utility of ion/molecule reactions in a DMS drift cell. For these reactions, dehydrated reactive precursor ions were initially formed and made to undergo annulation reactions with selected reagents within the timescale of the DMS separation. Careful study of the energies required for dissociation of the adducts confirmed the covalent nature of the newly formed bond; thus demonstrating the analytical utility of this approach. Graphical abstract.