Isobaric Interferences Research Articles

G.O.Joe: A new non‐commercial software tool for the processing of LA‐ICP‐MS trace element data

A common problem of trace element measurements by LA‐ICP‐MS is the existence of interferences that cannot be resolved instrumentally. The software G.O.Joe is developed to calculate trace element mass fractions in solid samples analysed by LA‐ICP‐MS, offering the opportunity to correct for isobaric interference (including mass bias) and abundance sensitivity. Designed as a platform‐independent web application, G.O.Joe is written in the Dart programming language and runs on all web browsers supported by Flutter (i.e., Chrome, Safari, Edge, Firefox) without the need for installation. G.O.Joe is freely accessible from any computer with an internet connection to facilitate immediate data evaluation and the efficient processing of large datasets (> 400 analyses). G.O.Joe features an intuitive user interface that simplifies the selection of peak and background signals, import of instrument settings and reference material compositions to convert the measured raw signals into element mass fractions. Key functions of G.O.Joe are presented by processing the analysis of tungstates and silicates (i.e., scheelite and garnet) including specific correction methods to demonstrate their large effect on interfered masses/isotopes achievable with only little effort. This study introduces G.O.Joe as a simple, time‐efficient and flexible software to significantly improve data quality in various trace element studies utilising LA‐ICP‐MS.

Testing the Ce Limit of Mass Bias Correction Using 145Nd/142Nd as Normalizing Ratio in Radiogenic Neodymium Isotope Analysis by MC-ICP-MS.

Neodymium isotopes are a powerful geochemical tool that has widely been used in terrestrial and extraterrestrial studies. Modern multicollector inductively coupled plasma mass spectrometers (MC-ICP-MS) allow fast, accurate, and precise analysis of the radiogenic Nd isotope ratio 143Nd/144Nd. These analyses comprise relatively high instrumental mass bias that is typically corrected for using the stable 146Nd/144Nd of 0.7219 and an exponential law. The instrument is usually tuned to optimize the operating conditions for isotope analysis, but this tuning is a trade-off primarily between signal intensity, stability, and accuracy. Alternative, more effective approaches for mass bias correction have been proposed that use 145Nd/142Nd as normalizing ratio. However, one drawback of using this ratio is that the efficient removal of Ce from Nd is required to minimize the effect of isobaric interference of 142Ce on 142Nd. Here, we analyzed international Nd and rock reference materials using a Thermo Scientific Neptune Plus MC-ICP-MS to evaluate the sensitivity of 145Nd/142Nd-based mass bias correction to varying Ce/Nd and in comparison with the commonly used 146Nd/144Nd-based correction. Our results show that the corrected 143Nd/144Nd of Ce-doped JNdi-1 and Ce-containing USGS BCR-2, NOD-A-1, and NOD-P-1 reference materials are insensitive to Ce/Nd of up ~1. The correction of instrumental mass bias with 145Nd/142Nd as a normalizing ratio yields, as previously suggested, improved trueness and precision of 143Nd/144Nd data in comparison with 146Nd/144Nd-based corrections, even under high Ce/Nd of to ~1. This allows improved optimization of signal intensity during instrument tuning, which is particularly useful for natural samples with low Nd content.

Improving methods for sample preparation of biological fluids by inductively coupled plasma mass spectrometry

This study presents the results of analyzing biological fluids using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) after applying various sample preparation methods. Optimal conditions for preparing biological fluids have been identified, which help minimize matrix effects and improve measurement accuracy. The most effective methods were selected considering the specifics of matrices and their interactions with analytical equipment. The study evaluated the contributions of spectral interferences to the analytical signal when using ICP-MS. It was found that the physical properties of acid solutions, such as viscosity, surface tension, density, and volatility, significantly affect the analysis results, introducing additional interferences and data distortions. The use of internal standards to eliminate spectral interferences was investigated. Criteria for choosing internal standards were established based on proximity to ionization potentials and mass characteristics, which allows for more accurate result correction and minimizes interference effects. Additionally, it was discovered that polyatomic ions play a significant role in enhancing analyte signals. This influence is due not to the background levels of elements in the samples or reagents, but to ions formed from matrix components in the samples. The study demonstrated that isobaric interferences caused by polyatomic ions significantly impact analytical accuracy. These findings contribute to improving sample preparation and analysis methods for biological fluids using ICP-MS, leading to more reliable and accurate measurements of element concentrations.

Actinide Elemental Ratios of Spent Nuclear Fuel Samples by Resonance Ionization Mass Spectrometry.

While resonance ionization mass spectrometry (RIMS) has demonstrated utility in measuring isotopic compositions of elements in complex matrices without the need for chemical separation to remove isobaric interferences, it has had limited application in measuring elemental compositions. The ability to determine elemental compositions via an in situ method like RIMS would be an exceptional asset in spent nuclear fuel analysis, where they are important in assessing reactor histories and whose chemical separation presents a radiological hazard. However, quantitative elemental analysis by RIMS requires special considerations because each element is ionized by its own set of lasers tuned to element specific resonant ionization wavelengths. We present the first comprehensive study of measuring elemental ratios by RIMS in spent nuclear fuel. All actinides produced by neutron capture are enhanced significantly radially from the center to the edge of a fuel pellet. This edge effect is not readily accessible by conventional bulk measurements.

Gas-Phase Reactivity of Actinides Monocations with NH3: ICP-MS Experiments Combined with a DFT Study.

The reactivity of actinide monocations (Th+, U+, Np+, Pu+, Am+, and Cm+) with NH3 gas was studied in the reaction cell of an inductively coupled plasma-mass spectrometer (ICP-MS). Only Th+, U+, Np+, and Cm+ react completely with NH3 to form AnNH+, contrary to Pu+ and Am+. Differences in reactivity are found between U+/Pu+, Pu+/Cm+, and Am+/Cm+, which could resolve isobaric interferences in ICP-MS. DFT calculations were performed across the first half of the actinide series. The calculated reaction energy between An+ and NH3 reproduces the experimental trends in reactivity with Th+ > Pa+ > U+ > Np+ > Ac+ > Cm+ > Pu+ > Am+. The reaction path involves the initial formation of an AnNH3+ adduct followed by N-H bond insertion with the formation of HAnNH2+ and H2AnNH+ intermediate species and subsequent H2 loss. The trend in reactivity across the actinides is largely due to the first energy barrier and formation of the HAnNH2+ intermediate species. This limiting step is energetically unfavorable for the Pu+ and Am+ cations. For these cations, the excitation energy required to achieve a reactive configuration with two non-f electrons available for bonding is too high.

B-284 Evaluation of Bupivacaine Metabolite Interference With Norfentanyl in a Liquid Chromatography Tandem Mass Spectrometry Assay in Neonatal Urine

Abstract Background Bupivacaine is a local anesthetic commonly used when administering epidurals during labor and delivery. Bupivacaine metabolite, N-desbutylbupivacaine (NDB), has recently been shown to cause isobaric interference in common urine norfentanyl quantifier and qualifier multiple reaction monitoring (MRM) transitions. This can interfere with the detection of prenatal fentanyl exposure in this vulnerable patient population, which is especially concerning if fentanyl is unexpected. A recent review of urine fentanyl reporting at our institution identified that the number of urine norfentanyl results reported as an interference comment is increasing. A chromatographic review determined this is due to the presence of an unidentified peak co-eluting just before norfentanyl in both the qualifier and quantifier MRM transitions. Most of these samples are from neonates. This study aimed to determine if NDB is the cause of the interfering peak in the urine norfentanyl MRM transitions and evaluate if other specimen types are also affected. Methods NDB standards were prepared and tested using the routine urine fentanyl assay performed by LC-MS/MS in our laboratory, using norfentanyl MRM transitions 233.1 --> 84.1 and 233.1 --> 150.1. Chromatography results were compared to patients with the interference. A retrospective data pull was performed to identify neonatal patients with a urine fentanyl result who also had an umbilical cord or meconium testing requested. Referring centers with patients with the interference comment were contacted to determine neonatal urine collection practices and if bupivacaine was used in their labor and delivery departments. Results NDB produced the same chromatographic pattern observed in the patient samples with norfentanyl interference. This confirmed NDB as the source of the interference. Centers with high rates of NDB interference were contacted and confirmed bupivacaine was routinely administered during labor and delivery at their facilities. Retrospective data analysis identified 577 urine samples with either paired umbilical cord (547) or meconium (30) samples. Of those, 478/577 (82.8%) urine samples displayed NDB interference, and norfentanyl could not be reported due to interference; however, 59 samples were positive for parent fentanyl. Of the 478 urine samples with NDB interference, 455 had a matching cord sample, and 23 had a matching meconium sample. Further examination identified 34/455 (7.5%) cord samples with matching urine samples that had NDB interference were positive for fentanyl. This suggests umbilical cord samples may be useful in some cases to resolve whether a neonate was exposed to fentanyl if NDB interference is observed in urine. Of the 23 paired urine/meconium samples, no positive meconium samples were associated with a urine sample with NDB interference. Conclusions Bupivacaine metabolite is commonly seen in the urine of neonates if bupivacaine is administered as an epidural. Chromatographic separation of bupivacaine metabolite from norfentanyl should be evaluated, especially for centers that receive neonatal samples.

Highly reliable LC-MS lipidomics database for efficient human plasma profiling based on NIST SRM 1950

Liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS)-based methods have become the gold standard methodology for the comprehensive profiling of the human plasma lipidome. However, both the complexity of lipid chemistry and LC-HRMS-associated data pose challenges to the characterization of this biological matrix. In accordance with the current consensus of quality requirements for LC-HRMS lipidomics data, we aimed to characterize the NIST® Standard Reference Material for Human Plasma (SRM 1950) using an LC-ESI(+/−)-MS method compatible with high-throughput lipidome profiling. We generated a highly curated lipid database with increased coverage, quality, and consistency, including additional quality assurance procedures involving adduct formation, within-method m/z evaluation, retention behavior of species within lipid chain isomers, and expert-driven resolution of isomeric and isobaric interferences. As a proof-of-concept, we showed the utility of our in-house LC-MS lipidomic database—consisting of 592 lipid entries—for the fast, comprehensive, and reliable lipidomic profiling of the human plasma from healthy human volunteers. We are confident that the implementation of this robust resource and methodology will have a significant impact by reducing data redundancy and the current delays and bottlenecks in untargeted plasma lipidomic studies.

Complete resolution across the neodymium/samarium isotopic envelope with a liquid sampling-atmospheric pressure glow discharge - Orbitrap mass spectrometer.

Nd and Sm isotope ratios play an important role in geological dating and as nuclear forensic signatures; however, the overlap of the respective 144, 148, 150 Nd/Sm isobars requires prior separations to be performed before analysis on typical MS platforms. The work presented here overcomes these isobaric interferences using ultrahigh-mass resolution to alleviate interference without prior chemical separations. A liquid sampling-atmospheric pressure glow discharge ion source was coupled to a standard, QExactive Focus Orbitrap mass spectrometer, providing a mass resolution of ~80 k. A Spectroswiss FTMS booster X2 data acquisition package was used to collect extended transients, providing much higher mass resolution; ~230 k and ~600 k are employed here for Nd and Sm isotopes. While the standard Orbitrap resolution is far greater than typical "atomic" MS platforms, it was insufficient to alleviate all isobars. The use of a resolution of ~230 k resulted in baseline separation across the entire isotopic envelope for both Nd and Sm. Isotope ratios obtained from Nd:Sm mixtures using high-resolution were equivalent to those found for individual-element solutions, while isotope ratios obtained at a resolution of ~80 k (standard for the OEM data system) showed large deviations. Use of ultrahigh-resolution is an attractive alternative to extensive chemical separations to alleviate severe isobaric interferences. Sufficient mass resolution greatly reduces/eliminates the need for sample manipulations (separations) before analysis while reducing costs and total analysis times.

LA-ICP-Q-MS/MS Re[sbnd]Os geochronology: A comparison of N2O and CH4 reaction gases

The ReOs isotope system can directly date sulphide formation, making it useful for ore deposit studies. Recent work has demonstrated that laser ablation inductively coupled tandem mass spectrometry (LA-ICP-MS/MS) can be used to effectively separate 187Re from 187Os during analysis by reacting Os with CH4 gas, allowing for in situ ReOs age determination of molybdenite. However, the age calculation often requires a significant interference correction of 187ReCH2+ on 187OsCH2+. Here, we demonstrate that N2O gas is a viable alternative reaction gas for in situ ReOs geochronology. In this new method, Os forms a tetra-oxide complex, while Re shows very low reactivity with the N2O reaction gas (∼0.15 %), reducing the isobaric interference correction requirement relative to the CH4 method. We compare results from both reaction gases across a range of molybdenite samples of different ages (spanning ca. 1700–300 Ma), demonstrating that the N2O method achieves greater precision and accuracy for young molybdenite samples (ca. 300 Ma) compared to CH4. In addition, we demonstrate that in situ ReOs is capable of dating high-Re pyrite (i.e., >10 ppm).

In situ Lu–Hf dating of allanite by LA-ICP-MS/MS: Implications for geochronology

Allanite is a common REE-rich accessory mineral found in various igneous and metamorphic rocks, and can record a variety of geological processes. Therefore, allanite geochronology has the potential to answer a range of important geological questions. Allanite U–Th–Pb geochronology is hampered by common open-system behavior in the system. In this study, we demonstrate the feasibility of in situ allanite Lu–Hf dating by LA–ICP–MS/MS. A total of nine allanite samples from different rock types (e.g., granite, pegmatite) were investigated. These allanite samples have ages ranging from ca. 2650 to ca.100 Ma, and Lu contents ranging from several to hundreds of μg g−1 levels and relatively high Lu/Hf ratios (> 30). At a mass shift of +82, the isobaric interferences 176Lu and 176Yb have extremely low reaction rates of ∼0.003 % and ∼ 0.0003 %, respectively, indicating the isobaric interference corrections are insignificant for the allanite samples (mean 175Lu/177Hf = ∼814; mean 172Yb/177Hf = ∼719). A two-step calibration strategy was proposed for the 176Lu/176Hf and 177Hf/176Hf ratio corrections using NIST SRM 610 (for instrument drift) and LE2808 (for matrix effect). The nine allanite samples contain common Hf contents (f176Hf) of ∼5 % to >90 %, and the data are plotted in inverse isochron diagrams. Unanchored inverse isochron ages exhibit a large deviation in accuracy (5–10 %), whilst anchored isochron ages have a better accuracy of <5 %. The uncertainty of anchor initial 176Hf/177Hf values was investigated and, in general, was insignificant (< 2.8 %) for samples with f176Hf < 80 %. Our results demonstrate that in situ allanite Lu–Hf dating by LA-ICP-MS/MS is feasible and can yield precise and accurate ages (< 5 %). Lu–Hf geochronometer captures the high-temperature process and may be more resistant during the late thermal event. Thus, it provides an alternative solution for those samples which are suffered by open-system behavior in U-Th-Pb system.

Detrital K-feldspar as a novel archive of continental crustal evolution using coupled in situ Rb[sbnd]Sr dating and Pb isotope analysis

Here we present in situ RbSr and Pb isotopic analysis of K-feldspar from the Shap Granite, (Cumbria, UK) and detrital K-feldspar from the associated Shap Wells Conglomerate Formation, to investigate the potential of the detrital K-feldspar record as an archive of crustal composition. We use a unique, collision cell – multi collector inductively coupled plasma tandem mass spectrometer to make the in situ isotope measurements, using ‘chemical resolution’ of 87Rb+ and 204Hg+ isobaric interferences on 87Sr+ and 204Pb+, achieved with SF6 and NH3 reaction gases, respectively. Using this technique, we successfully demonstrate that the majority of detrital K-feldspar RbSr ages, as well as initial Sr and Pb isotope ratios, from the Shap Wells Conglomerate are within uncertainty of those for parental Shap Granite K-feldspar (398 ± 1 Ma, n = 6). Some detrital K-feldspar grains record perturbed RbSr ages, reflecting post depositional alteration events. The majority of samples with disturbed RbSr ages carry distinct petrographic features evident in SEM imaging, prior to in situ dating, which indicates a means to help screen for reliable ages.We further illustrate the potential value of combined RbSr and Pb isotopic information preserved in K-feldspar to estimate the timing and chemical composition of juvenile continental crust formed in the past. Where UPb has been fractionated during juvenile crust formation, the initial Pb isotope ratio provided by the K-feldspar yields model crustal U/Pb (diagnostic of tectonic setting) and extraction age. The contrast in the U/Pb composition of juvenile crust formed in intraplate or subduction settings allows the model U/Pb ratios of the detrital K-feldspars to be used to constrain the style of juvenile crust formation. Additionally, the initial 87Sr/86Sr isotope ratio measured in detrital K-feldspar can be combined with the calculated crustal extraction age and RbSr K-feldspar age to model the Rb/Sr of the juvenile crustal protolith.

Assessment of emerging and persistent contaminants in an anthropogenic-impacted watershed: Application using targeted, non-targeted, and in vitro bioassay techniques

Emerging and persistent contaminants (EPC) pose a significant challenge to water quality monitoring efforts. Effect-based monitoring (EBM) techniques provide an efficient and systematic approach in water quality monitoring, but they tend to be resource intensive. In this study, we investigated the EPC distribution for various land uses using target analysis (TA) and non-target screening (NTS) and in vitro bioassays, both individually and integrated, in the upper Ping River Catchment, northern Thailand. Our findings of NTS showed that urban areas were the most contaminated of all land use types, although agriculture sites had high unexpected pollution levels. We evaluated the reliability of NTS data by comparing it to TA and observed varying inconsistencies likely due to matrix interferences and isobaric compound interferences. Integrating NTS with in vitro bioassays for a thorough analysis posed challenges, primary due to a scarcity of concentration data for key compounds, and potentially additive or non-additive effects of mixture samples that could not be accounted for. While EBM approaches place emphasis on toxic sites, this study demonstrated the importance of considering non-bioactive sites that contain toxic compounds with antagonistic effects that may go undetected by traditional monitoring approaches. The present work emphasizes the importance of improving NTS workflows and ensuring high-quality EBM analyses in future water quality monitoring programs.

Accuracy Improvement in the LA‐MC‐ICP‐MS Measurement of 87Sr/86Sr in Bioapatite Using Dentin of Carcharinus leucas (Bull shark) to Estimate 87Rb/85Rb Instrument Induced Fractionation

In situ 87Sr/86Sr microanalysis in bioapatite using laser ablation (LA‐)MC‐ICP‐MS is an essential tool for provenance studies, as enamel tissue build‐up records the regional Sr isotopic composition of ingested food and water sources. Several factors hamper the acquisition of reliable and precise 87Sr/86Sr data: isobaric interferences, elemental and isotopic fractionation of Rb and Sr, and the lack of certified reference materials. Here we thoroughly characterise several teeth from Carcharinus leucas (Bull shark) for the spatial distribution of Sr and Rb mass fraction by LA‐ICP‐Q‐MS, and their 87Sr/86Sr ratio by solution MC‐ICP‐MS, MC‐TIMS and LA‐MC‐ICP‐MS, and which were used subsequently as a reference material during laser ablation measurement of Sr isotope ratios in bioapatite. We establish a protocol to estimate the 85Rb/87Rb mass bias from the analysis of shark teeth that demonstrates that the common assumption of equal Sr and Rb instrument induced fractionation can lead to a systematic bias in 87Sr/86Sr isotope ratios. Using the shark teeth as an "external" reference material to measure βRb yielded 87Sr/86Sr compositions in unknown samples that are within approximately ‐42 ppm to +66 ppm of expected values, instead of approximately ‐50 ppm to +190 ppm if assuming βRb = βSr. Finally, this methodology was tested on fossil gomphotherid (Rhynchotherium sp.) enamel, allowing us to make preliminary inferences about its palaeobiogeography.

Electron Capture vs Transfer Dissociation for Site Determination of Tryptic Peptide Tyrosine Sulfation: Direct Detection of Fibrinogen Sulfation Sites and Identification of Novel Isobaric Interferences.

Tyrosine sulfation, an understudied but crucial post-translational modification, cannot be directly detected in conventional nanoflow liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) due to the extreme sulfate lability. Here, we report the detection of sulfate-retaining fragments from LC-electron capture dissociation (ECD) and nanoLC-electron transfer higher energy collision dissociation (EThcD). Sulfopeptide candidates were identified by Proteome Discoverer and MSFragger analysis of nanoLC-HCD MS/MS data and added to inclusion lists for LC-ECD or nanoLC-EThcD MS/MS. When this approach failed, targeted LC-ECD with fixed m/z isolation windows was performed. For the plasma protein fibrinogen, the known pyroglutamylated sulfopeptide QFPTDYDEGQDDRPK from the beta chain N-terminus was identified despite a complete lack of sulfate-containing fragment ions. The peptide QVGVEHHVEIEYD from the gamma-B chain C-terminus was also identified as sulfated or phosphorylated. This sulfopeptide is not annotated in Uniprot but was previously reported. MSFragger further identified a cysteine-containing peptide from the middle of the gamma chain as sulfated and deamidated. NanoLC-EThcD and LC-ECD MS/MS confirmed the two former sulfopeptides via sulfate-retaining fragment ions, whereas an unexpected fragmentation pattern was observed for the third sulfopeptide candidate. Manual interpretation of the LC-ECD spectrum revealed two additional isobaric identifications: a trisulfide-linked cysteinyl-glycine or a carbamidomethyl-dithiothreiotol covalent adduct. Synthesis of such adducts confirmed the latter identity.

Non-enantioselective, enantioselective, and two-dimensional liquid chromatography coupled with tandem mass spectrometry for the study of stereochemical disposition of oxylipins in cGMP-regulated hemin-treated platelets

Oxylipins are important low abundant signaling molecules in living organisms. In platelets they play a primary role in platelet activation and aggregation in the course of thrombotic events. In vivo, they are enzymatically synthesized by cyclooxygenases, lipoxygenases, or cytochrome P450 isoenzmes, resulting in diverse polyunsaturated fatty acid (FA) metabolites including hydroxy-, epoxy-, oxo-FAs, and endoperoxides with pro-thrombotic or anti-thrombotic effects. In a recent study, it was reported that hemin induces platelet death which was accompanied by enhanced reactive oxygen species (ROS) production (measured by flow cytometry) and lipid peroxidation (as determined by proxy using flow cytometry with BODIPY-C11 as sensor). Lipidomic studies further indicated significant changes of the platelet lipidome upon ex vivo hemin treatment, amongst others oxylipins were increased. The effect could be (at least partly) reversed by riociguat/diethylamine NONOate diethylammonium salt (DEA/NO) which modulates the soluble guanylate cyclase(sGC)-cGMP-cGMP-dependent protein kinase I(cGKI) signaling axis. In the original work, oxylipins were measured by a non-enantioselective UHPLC-tandem-MS assay which may not give the full picture whether oxylipin elevation is due to ROS or by enzymatic processes. We present here the study of the stereochemical disposition of hemin-induced platelet lipidome alterations using Chiralpak IA-U column with amylose tris(3,5-dimethylphenylcarbamate) chiral selector immobilized on 1.6 µm silica particles. It was found that the major platelet oxylipins 12-HETE, 12-HEPE and 14-HDoHE (from 12-LOX) and 12-HHT (from COX-1) were present in S-configuration indicating their enzymatic formation. On the other hand, both R and S enantiomers of 9- and 13-HODE, 11- and 15-HETE were detected, possibly due to enzyme promiscuity rather than non-specific oxidation (by ROS or autoxidation), as confirmed by multi-loop based two-dimensional LC-MS using selective comprehensive mode with achiral RPLC in the 1st dimension and chiral LC in the 2nd using a multiple heart-cutting interface. For 12-HETrE, a peak at the retention time of the R-enantiomer was ruled out as isobaric interference by 2D-LC-MS. In particular, arachidonic acid derivates 12(S)-HHT, 11(R)-HETE and 15(S)-HETE were found to be sensitive to hemin and cGMP modulation.

Exploration of metallic interferences pertinent to nuclear safeguards related uranium isotope ratio measurement on the Neoma MC-ICP-MS platform without the MS/MS option

In this paper we present basic observations regarding the formation and effect of various polyatomic metallic interferences (combinations of Pb, Al, Si, Mo, W, Fe, Sn, Ti, Ba, and Pt) on uranium isotopic ratios measured via a new Multi Collector – Inductively Coupled Plasma – Mass Spectrometer (MC-ICP-MS) platform: The ThermoFisher Scientific™ Neoma® (without the MS/MS® collision cell option). Our approach is to dope a uranium isotopic standard (IRMM-2020) with various quantities of the metallic elements, all of which have been previously identified as posing isobaric interferences during uranium isotope measurement, and then perform analyses in solution mode and by laser ablation (LA) MC-ICP-MS. As expected, there is considerable variability between the different elementally doped solution and the degree of perturbation exhibited by the uranium isotope standard. However, Pt appears to induce the most drastic shift for 234U/238U, 235U/238U, and 236U/238U. One unexpected result is that the presence of Pb, whether alone or in combination with Al and Si, appears to result in a reduction of the expected uranium signal. This effect was observed (and re-confirmed using a different cup configuration) on the Neoma® MC-ICP-MS during wet plasma analysis, but was not observed during dry plasma conditions (e.g. laser ablation sampling of dried IRMM-2020 containing Pb). Furthermore, the phenomenon was also not observed during dry plasma analysis on a NeptunePlus®. Further experiments will be necessary to fully understand the origin of this signal attenuation, and the results of our study highlight the need for continued investigation of the polyatomic interference issue as new MC-ICP-MS platforms are developed since our results clearly demonstrate that they can drastically skew the observed isotope ratios in sometimes unexpected directions. Lastly, the use of N2 during LA sampling appears to slightly increase the magnitude of the interferences compared to when only Ar is utilized as the carrier gas. This observation further highlights the importance of plasma conditions on interference formation.

Development of a high-throughput dual-stream liquid chromatography-tandem mass spectrometry method to screen for inhibitors of glutamate carboxypeptidase II.

Glutamate carboxypeptidase II (GCPII) catalyzes the hydrolysis of N-acetylaspartylglutamate (NAAG) to yield glutamate (Glu) and N-acetylaspartate (NAA). Inhibition of GCPII has been shown to remediate the neurotoxicity of excess Glu in a variety of cell and animal disease models. A robust high-throughput liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was needed to quantify GCPII enzymatic activity in a biochemical high-throughput screening assay. A dual-stream LC/MS/MS method was developed. Two parallel eluent streams ran identical HILIC gradient methods on BEH-Amide (2×30 mm) columns. Each LC channel was run independently, and the cycle time was 2min per channel. Overall throughput was 1min per sample for the dual-channel integrated system. Multiply injected acquisition files were split during data review, and batch metadata were automatically paired with raw data during the review process. Two LC sorbents, BEH-Amide and Penta-HILIC, were tested to separate the NAAG cleavage product Glu from isobaric interference and ion suppressants in the bioassay matrix. Early elution of NAAG and NAA on BEH-Amide allowed interfering species to be diverted to waste. The limit of quantification was 0.1pmol for Glu. The Z-factor of this assay averaged 0.85. Over 36 000 compounds were screened using this method. A fast gradient dual-stream LC/MS/MS method for Glu quantification in GCPII biochemical screening assay samples was developed and validated. HILIC separation chemistry offers robust performance and unique selectivity for targeted positive mode quantification of Glu, NAA, and NAAG.

Characterisation of titanium dioxide (nano)particles in foodstuffs and E171 additives by single particle inductively coupled plasma-tandem mass spectrometry using a highly efficient sample introduction system

This study addressed primarily the characterisation and quantification of titanium dioxide (TiO2) (nano)particles (NPs) in a large variety of commercial foodstuffs. The samples were purchased from local markets in Spain before the ban of TiO2 food additive (E171) in the EU. The analyses were carried out by single particle inductively coupled plasma-tandem mass spectrometry (spICP-MS/MS) in mass shift mode (oxidation of 48Ti to 48Ti16O (m/z = 64)) and using a highly efficient sample introduction system (APEX™ Ω). This novel analytical approach allowed accurate characterisation of a large panel of TiO2 NPs sizes ranging from ∼12 to ∼800 nm without isobaric interferences from 48Ca isotope, which is highly abundant in most of the analysed foodstuffs. TiO2 NPs were extracted from foodstuffs using sodium dodecyl sulphate (0.1%, w/v) and diluted with ultra-pure water to reach ∼ 1000 particles signals per acquisition. All the analysed samples contained TiO2 NPs with concentrations ranging from 1010 to 1014 particles kg−1, but with significant low recoveries compared to the total Ti determination. A selection of samples was also analysed using a similar spICP-MS/MS approach with a conventional sample introduction system. The comparison of results highlighted the improvement of the limit of detection in size (12 nm) by the APEX™ Ω system, providing nanoparticulate fractions ranging from ∼4% (cheddar sauce) up to ∼87% (chewing gum), which is among the highest nanoparticulate fractions reported in literature using a spICP-MS approach. In addition, two commercially available E171 additives were analysed using the previous approaches and other techniques in different European laboratories with the aim of methods inter-comparison. This study provides occurrence data related to TiO2 NPs in common commercial foodstuffs but it also demonstrates the potential of the novel analytical approach based on APEX™-ICP-MS/MS to characterise nano-size TiO2 particles in complex matrices such as foodstuffs.

Fully resolved high-precision measurement of 36S for sulfur reference materials.

Advances in sulfur isotope measurement techniques have led to increased analytical precision. However, accurate measurement of 36S remains a challenge. This difficulty arises primarily from unresolved isobaric interferences of 36SF5 + at m/z = 131u, 186WF4 2+ and 12C3F5 +, which lead to scale compression. Theoretically, unresolved interference with 2% relative intensity could cause 1‰ underestimation in a sample with real δ36S = +60‰. Our study develops an interference-free four-sulfur isotope measurement method by using the high-resolution mass spectrometer Panorama. The mass resolving power of Panorama allows the distinction of 186WF4 2+ and 12C3F5 + from 36SF5 +. The 186WF4 2+ relative intensity was initially 9.4% that of 36SF5 + but reduced to 1.5% through tuning, while 12C3F5 + relative intensity dropped from 74% to 40% after flushing with air. Three IAEA standards were analyzed with both Panorama and MAT 253. We obtained Δ36SIAEA-S-2 = 1.238 ± 0.040‰ and Δ36SIAEA-S-3 = -0.882 ± 0.030‰, relative to IAEA-S-1, from Panorama, and Δ36SIAEA-S-2 = 0.18 ± 0.02‰ and Δ36SIAEA-S-3 = 0.11 ± 0.14‰ from MAT 253, while δ34S values from the two instruments are consistent. The measurement discrepancies on 36S between Panorama and MAT 253 highlight the impact of scale compression due to unresolved isobaric interferences. Resolving this problem is crucial for accurate 36S analysis. We recommend replacing the filament material with rhenium, tuning the filament voltage, and avoiding carbon in instruments to eliminate or mitigate interferences. We propose future systematic efforts to calibrate the δ33S, δ34S, and δ36S of IAEA-S-1, IAEA-S-2, and IAEA-S-3 and advise bracketing all three reference materials in the measurement sequences, to enable calibration.

Multielement Detection of Nonmetals by Barium-Based Post-ICP Chemical Ionization Coupled to Orbitrap-MS.

Prevalence of F, Cl, S, P, Br, and I in pharmaceuticals and environmental contaminants has promoted standard-free quantitation using analyte-independent heteroatom responses in inductively coupled plasma (ICP)-MS. However, in-plasma ionization challenges and element-dependent isobaric interference removal methods have hampered the multielement nonmetal detection in ICP-MS. Here, we examine an alternative approach to enhance multielement detection capabilities. Analytes are introduced into an ICP leading to post-plasma formation of HF, HCl, H3PO3, H2SO4, HBr, and HI, which are then chemically ionized to BaF+, BaCl+, BaH2PO3+, BaHSO4+, BaBr+, and BaI+ via reactions with barium-containing ions supplied by a nanospray. Subsequent ion detection by high-resolution MS provides an element-independent approach for resolving isobaric interferences. We show that elemental response factors using these ions are linear within 2 orders of magnitude and independent of analytes' chemical structures. Using a single set of operating parameters, detection limits <1 ng/mL are obtained for Cl, Br, I, and P, while those for F and S are 1.8 and 6.2 ng/mL, respectively, offering improved multielement quantitation of nonmetals. Further, insights into ionization mechanisms indicate that the reactivities of reagent ions follow the order BaNO2+ > BaHCO2+ > Ba(H2O)n2+ ∼ BaCH3CO2+. Notably, the least reactive ions are generated directly by nanospray, suggesting that modification of these ions via interaction with plasma afterglow is critical for achieving good sensitivities. Moreover, our experiments indicate that the element-specific plasma products follow the order HF < H2SO4 ∼ HCl < H3PO3 ∼ HBr ∼ HI for their propensity to react with reagent ions. These insights provide guidelines to manage matrix effects and offer pathways to further improve the technique.