Chemical Ionization Research Articles

Direct Three-Dimensional Mass Spectrometry Imaging with Laser Ablation Remote Atmospheric Pressure Photoionization/Chemical Ionization.

The laser ablation remote atmospheric pressure photoionization/chemical ionization (LARAPPI/CI) platform coupled to an ultrahigh resolution quadrupole-time-of-flight (QToF) mass spectrometer was developed and employed for the first direct three-dimensional (3D) mass spectrometry imaging (MSI) of metabolites in human and plant tissues. Our solution for 3D MSI does not require sample modification or cutting into thin slices. Ablation characteristics of an optical system based on a diffraction optical element are studied and used for voxel stacking to directly remove layers of tissues. Agar gel, red radish, kiwi, human kidney cancer, and normal tissue samples were used for the tests of this new system. The 2D and 3D ion images vividly illustrate differences in the abundances of selected metabolites between cancerous and noncancerous regions of the kidney tissue and also between different parts of plant tissues. The LARAPPI/CI MSI setup is also the first example of the successful use of combined dopant-assisted atmospheric pressure photoionization (DA-APPI) and atmospheric pressure chemical ionization (APCI) ion source for mass spectrometry imaging.

Cool Classical EI - A New Standard in EI and Its Many Benefits.

GC-MS with Cold EI improves all of the central GC-MS performance aspects, but it is known mostly for its provision of enhanced molecular ions. This occasionally leads to the misconception that, like chemical ionization, Cold EI is a supplementary ion source to standard EI. However, Cold EI is a highly superior replacement ion source to standard EI. While Cold EI mass spectra are the most informative and fully compatible with mass spectral library (such as NIST) identification, in some cases, the Cold EI mass spectra with their enhanced molecular ions result in a "picture" that is not as one is used to seeing. In this paper, we describe the "Cool Classical EI" mode, which produces classical EI mass spectra like standard EI. The change of Cold EI into the Cool Classical EI mode is software-based, requires no hardware change, and can be achieved even during the analysis. Several mass spectra that were obtained in the Cool Classical EI mode are presented and compared with standard EI and Cold EI mass spectra. In this paper we further demonstrate and discuss several benefits that Cold EI brings that are retained while using Cool Classical EI, including (a) much faster speed of analysis, (b) uniform response, (c) extended range of compounds amenable for analysis, (d) improved sample identification, (e) elimination of ion source related peak tailing, (f) elimination of intraion-source degradation, and (g) better signal-to-noise ratio of the sample compounds.

Aerodynamic thermal breakup droplet ionization combined with a β-irradiation source for mass-spectrometric analysis of samples in a nonpolar solvent

A method is proposed for increasing the number of ions during mass-spectrometric analysis of samples in a nonpolar solvent (benzene). For this purpose, aerodynamic thermal breakup droplet ionization (ATBDI) with the impact of β-radiation on the aerosol droplets used in ATBDI was evaluated. This modification of the method, which we named β-ATBDI, allows to shift a nonvolatile analyte (trinitrotoluene in the negative ionization region and cocaine in the positive ionization region, as an example) into a gas phase as an aerosol at room temperature (in contrast to atmospheric pressure chemical ionization). In addition, β-ATBDI enables a researcher to distinguish mass spectrometric peaks of the compounds located in an aerosol droplet from compounds located outside the droplet, i.e., to identify background peaks. Also briefly discussed the ionization of two antibiotics—azithromycin in methylene chloride and sulfadiazine in salt water with β-ATBDI, ATBDI and electrospray ionization source.

MUSE spectroscopy of the high abundance discrepancy planetary nebula NGC\,6153

The abundance discrepancy problem in planetary nebulae (PNe) has long puzzled astronomers. NGC\,6153, with its high abundance discrepancy factor (ADF sim 10), provides a unique opportunity to study the chemical structure and ionisation processes within these objects. We aim to understand the chemical structure and ionisation processes in this high-ADF nebula by constructing detailed emission line maps and examining variations in electron temperature and density. This study also explores the discrepancies between ionic abundances derived from collisional and recombination lines, shedding light on the presence of multiple plasma components. We used the MUSE spectrograph to acquire IFU data covering the wavelength range 4600$-$9300 with a spatial sampling of 0.2 arcsec and spectral resolutions ranging from R = 1609 to R = 3506. We created emission line maps for 60 lines and two continuum regions. We developed a tailored methodology for the analysis of the data, including correction for recombination contributions to auroral lines and the contributions of different plasma phases. Our analysis confirmed the presence of a low-temperature plasma component in NGC\,6153. We find that electron temperatures derived from recombination line and continuum diagnostics are significantly lower than those derived from collisionally excited line diagnostics. Ionic chemical abundance maps were constructed, considering the weight of the cold plasma phase in the emission. Adopting this approach we found ionic abundances that could be up to 0.2 dex lower for those derived from CELs and up to 1.1 dex higher for those derived from RLs than in the case of a homogeneous emission. The abundance contrast factor (ACF) between both plasma components was defined, with values, on average, 0.9 dex higher than the ADF. Different methods for calculating ionisation correction factors (ICFs), including state-of-the-art literature ICFs and machine learning techniques, yielded consistent results. Our findings emphasise that accurate chemical abundance determinations in high-ADF PNe must account for multiple plasma phases. Future research should focus on expanding this methodology to a broader sample of PNe, with spectra deep enough to gather physical condition information of both plasma components, which will enhance our understanding of their chemical compositions and the underlying physical processes in these complex objects.

Computational and Experimental IM-MS Determination of the Protonated Structures of Antimalarial Drugs.

A combination of ion mobility-mass spectrometry (IM-MS) measurements and computational methods were used to study structural and physicochemical properties of a range of quinoline-based drugs: amodiaquine (AQ), cinchonine (CIN), chloroquine (CQ), mefloquine (MQ), pamaquine (PQ), primaquine (PR), quinacrine (QR), quinine (QN), and sitamaquine (SQ). In experimental studies, ionization of these compounds using atmospheric pressure chemical ionization (APCI) yields monoprotonated species in the gas phase while electrospray ionization (ESI) also produces diprotonated forms of AQ, CQ, and QR and also for PQ, SQ, and QN in the presence of formic acid as an additive. Comparison of the trajectory-method-calculated and experimental IM-derived collisional cross sections (CCSN2) were used to assign both the protonation sites and conformer geometry of all drugs considered with biases of 0.7-2.8% between calculated and experimental values. It was found that, in solution, AQ and QR are protonated at the ring nitrogen of the quinoline group, whereas the other drugs are protonated at the amine group of the alkyl chain. Finally, the conformers of [M + H]+ and [M + 2H]2+ assigned according to the lowest energies and CCSN2 calculations were used to calculate the pKa values of the antimalarial drugs and the relative abundance of these ions at different pH values that provided validation of the computational and experimental IM-MS results.

Thermal desorption – gas chromatography – mass spectrometry (TD-GC-MS) analysis of PFAS used in food contact materials

Per- and polyfluoroalkyl substances (PFAS) are used in food contact materials (FCMs), e.g. as production aids in the fabrication of PTFE based coatings for kitchenware or as additives in paper and board. Growing concerns about the environment and health related to PFAS have led to an increasing interest in monitoring PFAS levels in FCMs as well as their migration into food. In this study, method development for the analysis of PFAS by thermal desorption – gas chromatography – mass spectrometry (TD-GC-MS) was done. In addition to fluorotelomer alcohols (FTOHs), which are the only PFAS commonly analysed by GC-MS, it was proven that perfluorocarboxylic acids (PFCAs) and per- and polyfluoroether carboxylic acids (PFECAs) as well as their thermolysis products, perfluoroethers (PFEs) and perfluoroalkenes, can be analysed by GC-MS without prior derivatization. Screening for PFCAs and FTOHs was possible by electron impact ionization (EI) using group specific SIM fragments. Confirmation of identity has been done by EI scans as well as chemical ionization (CI) SIM measurements. LODs (limits of detection) of PFCAs, FTOHs and PFECAs in the TD-GC-MS instrument were in the low pg range. Thermal degradation of PFCAs and PFECAs during TD-GC-MS measurement was investigated.

Comparison of nitrogen and helium as carrier gases for determination of pesticide residues in foods via gas chromatography–tandem mass spectrometry with atmospheric pressure chemical ionization

The applicability of nitrogen as an alternative carrier gas to helium for the multiresidue analysis of pesticides using gas chromatography–tandem mass spectrometry with atmospheric pressure chemical ionization (GC–(APCI)MS/MS) was examined. The methods using both carrier gases were validated for 151 pesticides in foods at a spiking level of 0.01 ppm, maintaining identical conditions for both gases, including the GC column and carrier gas flow rate. The use of nitrogen resulted in slightly broader peaks and lower peak intensities that those observed upon using helium. However, sufficient sensitivity was achieved for all target compounds because of the high sensitivity of the GC–(APCI)MS/MS method. Further, target-compound separation was not significantly affected by the carrier gas type, and no interfering peaks were observed, demonstrating the high selectivity of the nitrogen-based method, even beyond the optimum linear velocity. Finally, the analytical performance of the nitrogen-based method was comparable to those of the helium-based method. Considering cost-effectiveness of nitrogen, this method is highly valuable in the event of helium shortages and for routine pesticide residue monitoring.

Heavy Water Microdroplet Surface Enriches the Lighter Isotopologue Impurities.

Water microdroplets promote unusual chemical reactions at the air-water interface. However, the interfacial structure of water microdroplets and its potential influence on chemical processes are still enigmatic. Here, we present evidence of in-droplet fractionation of water isotopologues. Employing a sonic spray, we atomized the heavy water (D2O, 99.9 atom % D) solution of three classes of organic compounds (basic, acidic, and neutral). The analytes were predominantly desorbed from the resulting droplet surface in protonated form rather than deuterated form, as detected by mass spectrometry. This result remained unaltered upon adding formic acid-d2 (DCOOD) to the droplet. Monitoring Dakin oxidation of benzaldehyde at the surface of binary microdroplets composed of 1:1 (v/v) D2O/H218O revealed the preferred formation of phenolate-16O over phenolate-18O. Atmospheric pressure chemical ionization mass spectrometric analysis of the vapor composition in the sprayed aerosol revealed the preferential evaporation of lighter water isotopologue impurities from the surface of heavy water microdroplets. These results indicate the enrichment of lighter water isotopologue impurities (HOD/H2O) on the surface of heavy water microdroplets, implying possible future developments for water isotopologue fractionation using microdroplets.

Effect of membrane properties on the odor emanating from training aids for explosive-detecting canines.

Canines are widely used for real-time detection of explosives and have proven to be on par with instrumental methods. Canines are thought to rely largely upon detection of volatile chemical constituents of the explosives, though not necessarily the explosive itself. Hence, it is crucial to understand the odor available to them as generated by training aids. Previous studies have established that the Training Aid Delivery Device (TADD) developed by SciK9 is a reliable training aid that reduces cross-contamination and doubles as a storage device. A TADD comprises a standardized container, a synthetic membrane, a membrane holder, and a lid. In the work presented, activated charcoal strips were placed above and below the TADD membrane to determine the relative amounts of volatiles emitted by dynamite (i.e., ethylene glycol dinitrate (EGDN) and trinitroglycerin (NG)). The strips were eluted and the extracts tested using gas chromatography-mass spectrometry in negative ion chemical ionization mode. A series of t-tests at 95% confidence level were performed to determine any differences in vapor composition above and below the membranes. Nine synthetic membranes and six glass fiber membranes were tested in this study. It was expected that the relative concentration of volatiles would remain the same on both sides of the membrane; however, selective removal of nitroglycerin by some membranes was observed. Synthetic membranes with larger pore sizes showed no alteration in the vapor composition. Both synthetic and glass fiber membranes did not show a significant change in relative concentration of the other volatile compound in dynamite, i.e., EGDN. Out of all the membranes tested, three synthetic membranes and four glass fiber membranes showed selective alteration in odor availability of nitroglycerin in dynamite. For training purposes, membranes that do not alter the vapor composition should be used in the training aid.

Omega-3 Long-Chain Polyunsaturated Fatty Acids in Nonseafood and Estimated Intake in the USA: Quantitative Analysis by Covalent Adduct Chemical Ionization Mass Spectrometry.

Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) play critical roles in human development and health. Their intake is often effectively estimated solely based on seafood consumption, though the high intake of terrestrial animal-based foods with minor amounts of LCPUFA may be significant. Covalent adduct chemical ionization (CACI) tandem mass spectrometry is one approach for de novo structural and quantitative analysis of minor unsaturated fatty acids (FA), for which standards are unavailable. Here, CACI-MS and MS/MS are used to identify and quantify minor omega-3 LCPUFA of terrestrial animal foods based on the application of measured response factors (RFs) to various FA. American mean intakes of pork, beef, chicken, and eggs contribute 20, 27, 45, and 71 mg/day of docosahexaenoic acid (DHA), respectively. The estimated intake of omega-3 DHA, eicosapentaenoic acid, and docosapentaenoic acid from nonseafood sources is significant, at 164, 103, and 330 mg/day, greater than most existing estimates of omega-3 LCPUFA intake.

Liquid chromatography-tandem mass spectrometry for determination of fingolimod and its active metabolite fingolimod phosphate in whole blood of patients with multiple sclerosis.

Fingolimod is an oral drug for the escalation of treatment of relapsing-remitting multiple sclerosis in patients with persistent disease activity on first-line drugs or in patients with rapidly progressive severe relapsing-remitting multiple sclerosis. An ultra-high-performance liquid chromatography-tandem mass spectrometry method for determining the concentrations of fingolimod and its active metabolite fingolimod phosphate in whole blood has been developed and validated. The advantages of this method are the easy, fast and cheap sample preparation using protein precipitation from blood with a mixture of acetonitrile-methanol (40:60, v/v). Chromatographic separation was performed on a ultra-high performance liquid chromatography BEH C18 1.7 μm (100 × 2.1mm) column. Two modes of ionization, electrospray ionization and atmospheric pressure chemical ionization, were tested and compared. For validation, the electrospray ionization mode was chosen. As internal standard, isotopically labeled fingolimod-D4 was used to quantify the analytes. The method was validated according to the rules of the European Medicines Agency. The coefficients of variation for fingolimod were in the range of 1.13-11.88%, and the recovery was 98.80-106.00%. The coefficients of variation for fingolimod phosphate were in the range of 2.73-9.31%, and the recovery was 90.08-107.00%. The method is quite easy and fast and can be used for routine analysis.

Direct detection of monoterpenes in evacuated air atmospheres by glow discharge plasma source for mass spectrometry

Some compounds, including the monoterpenes, are difficult to be analyzed by chemical ionization mass spectrometry (CI-MS) mass spectrometry because of having distinct chemical features of unsaturated bonds in relatively large molecule, which is responsible for occurring fragmentation of molecular ions. A direct detection of monoterpenes, including monocyclic, bicyclic and oxygenated (acyclic), was carried out using a soft plasma ionization (SPI) source combined with a q-mass spectrometer (q-MS). Detectable signals for monoterpenes were examined in an ambient air discharge plasma when varying the discharge parameters, such as discharge pressure (0.4–3.0 kPa) and sample/carrier pressure ratio (R = 5–100%). Furthermore, to consider the ionization reactions in detail, nitrogen gas was also used as the discharge gas (carrier gas). Monoterpenes, including cross-linked bicyclic (α-pinene and β-pinene) and oxygenated (linalool, geraniol, nerol and eucalyptol), in which their simple spectrum patterns can be obtained with little or no fragmentation at an ambient air pressure of several kPa, has successfully conducted by the pulsed dc SPI-MS. To our knowledge, this is the first report demonstrating that the spectrum pattern of monoterpenes could be directly detected without any complicated fragmentation of analyte ions in the SPI source.

LC-MS/MS quantification of Δ8-THC, Δ9-THC, THCV ISOMERS and their main metabolites in human plasma.

In recent years, potential therapeutic applications of several different cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC), its isomer Δ8-THC and Δ9-tetrahydrocannabivarin (Δ9-THCV), have been investigated. Nevertheless, to establish dose-effect relationship and to gain knowledge of their pharmacokinetics and metabolism, sensitive and specific analytical assays are needed to measure these compounds in patients. For this reason, we developed and validated an online extraction high-performance liquid chromatography- tandem mass spectrometry (LC/LC-MS/MS) method for the simultaneous quantification of 13 cannabinoids and metabolites including the Δ8 and Δ9 isomers of THC, THCV and those of their major metabolites in human plasma. Plasma was fortified with cannabinoids at varying concentrations within the working range of the respective compound and 200 µL were extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC/LC-atmospheric pressure chemical ionization (APCI)-MS/MS running in the positive multiple reaction monitoring (MRM) mode. The lower limit of quantification ranged from 0.5 to 2.5 ng/mL and the upper limit of quantification was 400 ng/mL for all analytes. Inter-day analytical accuracy and imprecision ranged from 82.9 to 109% and 4.3 to 20.3% (coefficient of variance), respectively. Of 534 plasma samples following controlled oral administration of Δ8-THCV, 236 were positive for Δ8-THCV (median; interquartile ranges: 3.5 ng/mL; 1.8 - 11.9 ng/mL), 383 for the major metabolite (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabivarin (Δ8-THCV-COOH) (95.4 ng/mL; 20.7 - 328 ng/mL), 260 for (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (Δ9-THCV-COOH) (5.8 ng/mL; 2.5 - 16.1 ng/mL), 157 for (-)-11-hydroxy-Δ8-tetrahydrocannabivarin (11-OH-Δ8-THCV) (1.7 ng/mL; 1.0 - 3.7 ng/mL), 49 for Δ8-THC-COOH (1.7 ng/mL; 1.4 - 2.3 ng/mL) and 42 for Δ9-THCV (1.3 ng/mL; 0.8 - 1.6 ng/mL). We developed and validated the first LC/LC-MS/MS assay for the specific quantification of Δ8-THC, Δ9-THC and THCV isomers and their respective metabolites in human plasma. Δ8-THCV-COOH, 11-hydroxy-Δ8-THCV and Δ9-THCV-COOH were the major Δ8-THCV metabolites in human plasma after oral administration of 98.6% pure Δ8-THCV.

Gas chromatography/mass spectrometry analysis of reaction products of Chemical Weapons Convention-related 2-(N,N-dialkylamino)ethylchlorides with 2-(N,N-dialkylamino)ethanols.

The Chemical Weapons Convention (CWC) mandates rigorous screening of chemical weapons and their potential degradation/reaction products, which is essential to identify such products in suspected samples. The reaction between 2-(N,N-dialkylamino)ethylchlorides and 2-(N,N-dialkylamino)ethanols (precursors/degradation products of VX agents) produces a new class of reaction products that are not explored. The reaction products, bis(2-N,N-dialkylaminoethyl)ethers (1-10), were synthesized using established synthetic procedures, and gas chromatography/mass spectrometry (GC/MS) (electron ionization [EI] and chemical ionization [CI]) methods were developed for their identification. The GC/MS experiments were performed on an Agilent GC/MSD system using an HP-5MS capillary column. Methane gas was used as the CI reagent gas for GC/CIMS experiments. GC/retention index (RI) values of 1-10 were calculated using the retention times of the hydrocarbon mixture and the analytes. The GC/EI spectra of 1-10 exhibited [M-H]+ ions and distinctive fragments that provided valuable structural information. The selective fragmentation of the alkyl groups on nitrogen facilitated the discrimination of possible isomeric compounds. Interpretation of EI fragments in the high mass region is important for unambiguous identification of 1-10, because the major ions significantly match other CWC-related compounds containing the 2-(N,N-dialkylaminoethyl) group. GC/CI (methane) spectra included M+., [M + H]+, [M-H]+, reagent-specific adduct ions, and a few structure-indicative fragments. The spiking experiments in soil and water samples revealed that the target analytes were stable, easily extractable, and detectable using GC/MS. The reaction products, 1-10, could be successfully synthesized and characterized using GC/MS (EI and CI). The GC/MS and GC/RI data provide important insights into the unambiguous identification of the target molecules in challenging CWC verification and are helpful in participation in the Organization for the Prohibition of Chemical Weapons proficiency tests.

Serum hydroxycotinine was associated with chronic kidney disease (CKD): a cross-sectional study based on NHANES

Objective Smoking has been suggested as a modifiable and cardiovascular risk factor for chronic kidney disease (CKD). Although long-term smoking has been associated with CKD, the potential relationship between its metabolite hydroxycotinine and CKD has not been clarified. Methods A total of 8,544 participants aged 20 years and above from the National Health and Nutrition Examination Survey (NHANES) 2017 - March 2020 were enrolled in our study. CKD was defined by estimated glomerular filtration rate (eGFR) < 60 mL/(min*1.73 m2). Serum hydroxycotinine was measured by an isotope-dilution high-performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometric (ID HPLC-APCI MS/MS) method with a lower limit of detections (LLOD) at 0.015 ng/mL. The non-linear relationship was explored with restricted cubic splines (RCS). Pearson’s correlation coefficient and a multivariate logistic regression model were used for correlation analysis. Results Serum hydroxycotinine and eGFR were negatively correlated in both non-CKD group (r= −0.05, p < 0.001) and CKD group (r= −0.04, p < 0.001). After serum hydoxycotinine dichotominzed with LLOD, serum hydroxycotinine ≥ 0.015 ng/mL was negatively correlated with eGFR not only in non-CKD group (r = −0.05, p < 0.001) but also in CKD group (r = −0.09, p < 0.001). After adjusting for comprehensive confounders, results from the multivariate logistic regression analysis showed that participants with serum hydroxycotinine ≥ 0.015 ng/mL had increased odds of CKD (OR = 1.505, p < 0.001). Conclusions Serum hydroxycotinine might be positively associated with CKD. Further study is warranted to find the right concentration of hydroxycotinine to measure the CKD.

A New Photoionization-Induced Substitution Reaction Chemical Ionization Time-of-Flight Mass Spectrometry for Highly Sensitive Detection of Trace Exhaled Ethylene

A New Photoionization-Induced Substitution Reaction Chemical Ionization Time-of-Flight Mass Spectrometry for Highly Sensitive Detection of Trace Exhaled Ethylene

High enrichment factors in chemical analysis of progestins and in bioassays: insights beyond trace levels.

Concerns are growing about adverse effects of progestins on biota, even at ultra-trace concentrations. The enrichment factor (EF) from extraction of analytes in environmental samples that is needed for sample pre-concentration can affect not only performance of the analytical method but also the matrix effect. Therefore, the present study aimed to assess the influence of high sample EF on performance of the high-performance liquid chromatography with atmospheric pressure chemical ionization and photoionization coupled with high-resolution mass spectrometry (HPLC-APCI/APPI-HRMS) method for analysis of progestins in waste water treatment plant (WWTP) effluents and surface waters and analysis of (anti-)progestogenic activities measured by (anti-)PR-CALUX bioassays. The results showed that HPLC-APCI/APPI-HRMS coupled with solid-phase extraction and a high EF (33,333 Lwater/Lextract) enabled the detection of more compounds compared to samples with lower sample EF (10,000 Lwater/Lextract). The matrix effect did not increase proportionally compared to lower EFs (10,000 and 16,666 Lwater/Lextract), and lower limits of quantification were achieved in WWTP effluents and surface waters. The results of bioassays have shown that relative EF of 25 Lwater/Lbioassay appears high enough to detect progestogenic activity in treated waste water. Our study is one of the first to provide insights into sample pre-concentration in analysis of progestins and progestogenicity in aquatic environments.

Extending the Range of Detectable Trace Species with the Fast Polarity Switching of Chemical Ionization Orbitrap Mass Spectrometry.

Chemical ionization (CI) atmospheric pressure interface mass spectrometry is a unique analytical technique for its low detection limits, softness to preserve molecular information, and selectivity for particular classes of species. Here, we present a fast polarity switching approach for highly sensitive online analysis of a wide range of trace species in complex samples using selective CI chemistries and high-resolution mass spectrometry. It is achieved by successfully coupling a multischeme chemical ionization inlet (MION) and an Orbitrap Fourier transform mass spectrometer. The capability to flexibly combine ionization chemistries from both polarities effectively extends the detectability compared to using only one ionization chemistry, as commonly used positive and negative reagent ions tend to be sensitive to different classes of species. We tested the performance of the MION-Orbitrap using reactive gaseous organic species generated by α-pinene ozonolysis in an environmental chamber and a standard mixture of 71 pesticides. Diethylammonium and nitrate are used as reagent ions in positive and negative polarities. We show that with a mass resolving power of 280,000, the MION-Orbitrap can switch and measure both polarities within 1 min, which is sufficiently fast and stable to follow the temporal evolution of reactive organic species and the thermal desorption profile of pesticides. We detected 23 of the 71 pesticides in the mixture using only nitrate as the reagent ion. Facilitated by polarity switching, we also detected 47 pesticides using diethylammonium, improving the total number of detected species to 59. For reactive organic species generated by α-pinene ozonolysis, we show that combining diethylammonium and nitrate addresses the need to measure oxygenated molecules in atmospheric environments with a wide range of oxidation states. These results indicate that the polarity switching MION-Orbitrap can promisingly serve as a versatile tool for the nontargeted chemical analysis of trace species in various applications.

Simultaneous quantification of terpenes and cannabinoids by reversed-phase LC-APCI-MS/MS in Cannabis sativa L. samples combined with a subsequent chemometric analysis

Cannabis sativa L. has been the most discussed medicinal plant in recent years. In particular, the dynamic shift from a formerly illicit and tightly controlled substance to a plant recognized for both medicinal and recreational purposes has brought C. sativa into the global spotlight. Due to the ongoing international legalization processes, fast and convenient analytical methods for the quality control of C. sativa flowers for medicinal and recreational purposes are of tremendous interest. In this study, we report the development and validation of a liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based method applying atmospheric pressure chemical ionization (APCI) to fully quantify 16 terpenes and 7 cannabinoids including their acidic forms by a single chromatographic method. The method presented here is unique and simple, as it eliminates the need for derivatization reactions and includes the unconventional analysis of volatile compounds by liquid chromatography. Samples were prepared by a simple and fast ethanolic extraction. Separation was accomplished within 25 min on a reversed-phase C18 column. Method validation was conducted according to international guidelines regarding selectivity, accuracy, precision, robustness, and linearity. Detection was done in multiple reaction monitoring, which allowed the simultaneous quantification of co-eluting analytes applying two selective mass transitions. In addition, due to reproducible in-source decarboxylation, the acidic forms of cannabinoids were reliably quantified using mass transitions of the neutral forms. The accuracy given as the bias was below 15% for all analytes. Matrix effects for cannabinoids were studied by spiking Humulus lupulus extracts with the analytes at varying concentrations. APCI did not show susceptibility toward ion suppression or enhancement. In addition, the recovery effect after spiking was between 80 and 120% for terpenes. Further, 55 authentic C. sativa extracts were fully quantified, and the obtained results for the terpene profiles were compared to state-of-the-art gas chromatography coupled to flame ionization detection. Comparable results were achieved, emphasizing the method’s applicability for cannabinoids and terpenes. Further, acquired metabolite patterns for C. sativa samples were studied, identifying a relationship between cannabinoid and terpene patterns, as well as the abundance of myrcene in CBD-dominant C. sativa strains.Graphical

Determination of Patulin in Apple Juice and Apple-Derived Products Using a Robotic Sample Preparation System and LC-APCI-MS/MS.

Patulin, a toxic mycotoxin, can contaminate apple-derived products. The FDA has established an action level of 50 ppb (ng/g) for patulin in apple juice and apple juice products. To effectively monitor this mycotoxin, there is a need for adequate analytical methods that can reliably and efficiently determine patulin levels. In this work, we developed an automated sample preparation workflow followed by liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) detection to identify and quantify patulin in a single method, further expanding testing capabilities for monitoring patulin in foods compared to traditional optical methods. Using a robotic sample preparation system, apple juice, apple cider, apple puree, apple-based baby food, applesauce, fruit rolls, and fruit jam were fortified with 13C-patulin and extracted using dichloromethane (DCM) without human intervention, followed by an LC-APCI-MS/MS analysis in negative ionization mode. The method achieved a limit of quantification of 4.0 ng/g and linearity ranging from 2 to 1000 ng/mL (r2 > 0.99). Quantitation was performed with isotope dilution using 13C-patulin as an internal standard and solvent calibration standards. Average recoveries (relative standard deviations, RSD%) in seven spike matrices were 95% (9%) at 10 ng/g, 110% (5%) at 50 ng/g, 101% (7%) at 200 ng/g, and 104% (4%) at 1000 ng/g (n = 28). The ranges of within-matrix and between-matrix variability (RSD) were 3-8% and 4-9%, respectively. In incurred samples, the identity of patulin was further confirmed with a comparison of the information-dependent acquisition-enhanced product ion (IDA-EPI) MS/MS spectra to a reference standard. The metrological traceability of the patulin measurements in an incurred apple cider (21.1 ± 8.0 µg/g) and apple juice concentrate (56.6 ± 15.6 µg/g) was established using a certified reference material and calibration data to demonstrate data confidence intervals (k = 2, 95% confidence interval).