Skimmer Cone Research Articles

Simple setup for gas-phase H/D exchange mass spectrometry coupled to electron transfer dissociation and ion mobility for analysis of polypeptide structure on a liquid chromatographic time scale.

Gas-phase hydrogen/deuterium exchange (HDX) is a fast and sensitive, yet unharnessed analytical approach for providing information on the structural properties of biomolecules, in a complementary manner to mass analysis. Here, we describe a simple setup for ND3-mediated millisecond gas-phase HDX inside a mass spectrometer immediately after ESI (gas-phase HDX-MS) and show utility for studying the primary and higher-order structure of peptides and proteins. HDX was achieved by passing N2-gas through a container filled with aqueous deuterated ammonia reagent (ND3/D2O) and admitting the saturated gas immediately upstream or downstream of the primary skimmer cone. The approach was implemented on three commercially available mass spectrometers and required no or minor fully reversible reconfiguration of gas-inlets of the ion source. Results from gas-phase HDX-MS of peptides using the aqueous ND3/D2O as HDX reagent indicate that labeling is facilitated exclusively through gaseous ND3, yielding similar results to the infusion of purified ND3-gas, while circumventing the complications associated with the use of hazardous purified gases. Comparison of the solution-phase- and gas-phase deuterium uptake of Leu-Enkephalin and Glu-Fibrinopeptide B, confirmed that this gas-phase HDX-MS approach allows for labeling of sites (heteroatom-bound non-amide hydrogens located on side-chains, N-terminus and C-terminus) not accessed by classical solution-phase HDX-MS. The simple setup is compatible with liquid chromatography and a chip-based automated nanoESI interface, allowing for online gas-phase HDX-MS analysis of peptides and proteins separated on a liquid chromatographic time scale at increased throughput. Furthermore, online gas-phase HDX-MS could be performed in tandem with ion mobility separation or electron transfer dissociation, thus enabling multiple orthogonal analyses of the structural properties of peptides and proteins in a single automated LC-MS workflow.

Determination of boron isotope compositions of geological materials by laser ablation MC-ICP-MS using newly designed high sensitivity skimmer and sample cones

The effects of addition of nitrogen gas with use of three different combinations of sample and skimmer cones on the performance of LA-MC-ICP-MS for in situ B isotope ratio measurements were investigated in detail. Compared to the standard arrangement (H skimmer cone+standard sample cone), sensitivities of B isotopes were improved by a factor of 2.4 and 3.8 with use of X skimmer cone+standard sampler cone and the X skimmer cone+Jet sample cone, respectively. The best within-run precision (2s) of 11B/10B was approximately 50ppm for B4 reference material (B content=31,400μg/g) with use of X skimmer cone+Jet sample cone. It was found that different cone combinations had significant effects on the instrument mass bias, but had little effect on the precisions of B isotope ratios. Addition of nitrogen (2–4ml/min) in the central channel gas did not improve the sensitivity of B. However, significant wider ion axial distribution profile and more stable mass-bias for B isotope ratios were evident. Under selected optimum conditions, good agreements between the measured δ11B values and the reference values were obtained for the international reference minerals (B4, Dravite, Elbaite, IMMRB1 and Schorl), the NIST SRM 610–612 synthetic soda-lime glasses and the MPI-DING glasses (GOR-128-G, GOR-132-G, and StHs6/80). It was found that for low-B containing (11ppm and 31ppm) materials, the precisions (2s) of 11B/10B can be improved by a factor of 2–10 by using the newly designed X-skimmer cone and Jet sample cone, compared to that of using the standard cones. The international reference mineral Danburite (δ11B of −14.92±6.77 2SD, n=32) showed a significant non-uniformity of B isotope ratio distribution. Our first boron isotopic results from standards GSD-1G (δ11B: 11.92±1.03, n=30), GSE-1G (δ11B: 1.63±0.32, n=30), GP-4 (δ11B: −5.85±1.01, n=40) and DD-1 (δ11B: −13.21±0.56, n=35) showed these materials were fairly homogeneous in boron isotope ratios, making them as good candidates as reference materials. The proposed LA-MC-ICPMS method is suitable for the direct determination of B isotope ratio in a variety of geological materials.

Accurate Analysis of Chromium in Foodstuffs by Using Inductively Coupled Plasma Mass Spectrometry with a Collision-Reaction Interface

Food is a common source of chromium (Cr) exposure. However, it is difficult to analyze Cr in complex food matrices by using inductively coupled plasma mass spectrometry (ICP-MS) because the major isotope, <TEX>$^{52}Cr$</TEX>, is masked by interference generated by the sample matrix and the plasma gas. Among the systems available to minimize interference, the recently developed collision-reaction interface (CRI) has a different structure relative to that of other systems (e.g., collision cell technology, octopole reaction system, and dynamic reaction cell) that were designed as a chamber between the skimmer cone and quadrupole. The CRI system introduces collision or reaction gas directly into the plasma region through a modified hole of skimmer cone. We evaluated the use of an CRI ICP-MS system to minimize polyatomic interference of <TEX>$^{52}Cr$</TEX> and <TEX>$^{53}Cr$</TEX> in various foodstuffs. The <TEX>$^{52}Cr$</TEX> concentrations measured in the standard mode were 2-3 times higher than the certified values. This analytical method based on an ICP-MS system equipped with a CRI of helium gas was effective for Cr analysis in complex food matrices.

Matrix Assisted Ionization Vacuum (MAIV), a New Ionization Method for Biological Materials Analysis Using Mass Spectrometry

The introduction of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) for the mass spectrometric analysis of peptides and proteins had a dramatic impact on biological science. We now report that a wide variety of compounds, including peptides, proteins, and protein complexes, are transported directly from a solid-state small molecule matrix to gas-phase ions when placed into the vacuum of a mass spectrometer without the use of high voltage, a laser, or added heat. This ionization process produces ions having charge states similar to ESI, making the method applicable for high performance mass spectrometers designed for atmospheric pressure ionization. We demonstrate highly sensitive ionization using intermediate pressure MALDI and modified ESI sources. This matrix and vacuum assisted soft ionization method is suitable for the direct surface analysis of biological materials, including tissue, via mass spectrometry.

Standardless determination of Nd isotope ratios in glasses and minerals using laser-ablation multiple-collector inductively coupled plasma mass spectrometry with a low-oxide molecular yield interface setup

We investigated an appropriate instrumental setup for a laser-ablation multiple-collector inductively coupled plasma mass spectrometer (LA-MC-ICP-MS) and found that a reduced oxide setting allowed accurate and precise analysis of Nd isotope ratios in samples with or without concomitant interfering elements. We used an Aridus II solution–excimer laser dual-intake system. The ICP interface used a normal sample and skimmer cones with the torch shield switched off and an additional large interface rotary pump. The setting accomplished reduced oxide levels NdO+/Nd+ 0.01–0.05%, without significant sacrifice of the instrumental sensitivity (∼70%). Oxide molecular ions for the lighter elements were negligible and accurate internal mass bias corrections were achieved for both Sm and Nd using isotopic ratios derived from thermal ionization mass spectrometry measurements. This report reveals a novel setup that requires no external mass bias corrections (standardless analysis) for Sm and Nd isotope analyses by both solution- and LA-MC-ICP-MS methods. Solution analysis of La Jolla Nd standard gave a 143Nd/144Nd ratio of 0.511860 ± 0.000026, which is in excellent agreement with the reference value (relative deviation (RD) = +6 ppm). JMC Nd standard solution yielded a 143Nd/144Nd ratio of 0.512216 ± 0.000044 (RD = −14 ppm) while a Sm-doped JMC solution showed 0.512211 ± 0.000030 (RD = −23 ppm). For LA analyses, the observed ratios and RDs were 143Nd/144Nd = 0.511921 ± 0.000013 (RD = −12 ppm) for NIST SRM 610 glass standard (430 ppm Nd/453 ppm Sm); 0.512490 ± 0.000018 (RD = +14 ppm) for Durango apatite (1121 ppm Nd/147 ppm Sm); 0.512200 ± 0.000009 (RD = −26 ppm) for Fish Canyon Tuff sphene; 0.512232 ± 0.000003 (RD = +65 ppm) for EDR monazite and 0.512890 ± 0.000147 (RD = +34 ppm) for groundmass of a St. Helena lava (22.7 ppm Nd/∼5.01 ppm Sm). All measurements were in good agreement with the reference values. Examinations of Sm/Nd elemental fractionation have also been made and we confirmed that this originated from the ICP interface region rather than at the laser ablation site.

Evaluation of a Collision-Reaction Interface (CRI) for Carbon Effect Correction on Chromium Determination in Environmental Samples by ICP-MS

Spectral interferences in inductively coupled plasma quadrupole mass spectrometry (ICP-MS) may affect several trace element analyses. In this work, the performance of a collision-reaction interface (CRI) for correction of spectral interferences on chromium determination at m/z 52 affected by 40Ar12C+ in a rich-carbon medium was evaluated. Hydrogen or He gases were introduced through sampler or skimmer cones of the CRI for promoting collisions and reactions. Background equivalent concentrations (BEC) and signal-background ratios (SBR) were the chosen parameters for evaluating CRI performance. It was observed that the introduction of both gases through the sampler cone was not effective considering the maximum gas flow rate evaluated at 140 mL min−1. The best condition to reduce polyatomic interferences caused by carbon containing species was obtained while introducing 60 mL min−1 of H2 through the skimmer cone. The trueness of the developed procedure was checked by 52Cr+ determination in certified reference materials. Sequential extractions in acetic acid and ammonium acetate (carbon sources) media, according to the Bureau Communautaire de Référence (BCR) of the Commission of the European Communities, was employed for BCR 701 (Lake Sediment) and microwave-assisted digestion was applied for Sewage Sludge from Industrial Origin (BCR 146 R). The feasibility of the CRI to overcome spectral interferences caused by molecular ions containing carbon on 52Cr+ determined by ICP-MS was demonstrated.

Investigation into the behavior of metal-argon polyatomic ions (MAr+) in the extraction region of inductively coupled plasma-mass spectrometry

The abundances of metal-argon polyatomic ions (MAr+) are determined in inductively coupled plasma-mass spectrometry (ICP-MS). The ratios of MAr+ abundance to that for M+ ions are measured experimentally. These ratios are compared to expected values, calculated for typical plasma conditions using spectroscopic data. For all metals studied (Ti, V, Cr, Mn, Fe, Co, Ni, Cu, and Zn), the measured ratios are significantly lower than the calculated ratios. Increasing the plasma potential (and thereby increasing the ion kinetic energy) by means of a homemade guard electrode with a wide gap further reduces the MAr+/M+ ratio. Implementing a skimmer cone designed for high transmission of light ions increases the MAr+ abundance. Considering this evidence, the scarcity of MAr+ ions is attributed to collision induced dissociation (CID), likely due to a shock wave at the tip of or in the throat of the skimmer cone.

Assessment of Polyatomic Interferences Elimination Using a Collision Reaction Interface (CRI) for Inorganic Analysis of Fuel Ethanol by ICP-QMS

The effectiveness of a collision-reaction interface (CRI) as instrumental device and the addition of oxygen in the composition of auxiliary gas were evaluated to minimize polyatomic species generated in plasma gas caused by direct introduction of fuel ethanol samples through spray chambers in inductively coupled plasma quadrupole mass spectrometry (ICP-QMS). The oxygen flow-rate was optimized as a compromise among signal counts, signal to background ratio (SBR), and background equivalent concentration (BEC). For 12.5 mL min−1 O2, ethanol samples diluted 20 times were introduced into the plasma and deposits of carbon compounds on the sampler and/or skimmer cones were not observed. The performance of CRI using H2 and He inserted through the sampler or skimmer cones was evaluated. Hydrogen gas added through the skimmer cone was more efficient to reduce blank and BEC values. This strategy was necessary to eliminate spectral interferences caused by 40Ar12C+, 40Ar16O+, 12C16O+, at isotopes 52Cr+, 56Fe+, 28Si+ and 24Mg+, respectively. Using matrix-matching calibration and Y internal standard, the optimized method was applied to the determination of Al, Ba, Co, Cr, Cu, Fe, Mg, Mn, Mo, Na, Ni, Pb, Sb, Si, V, and Zn in fuel ethanol. Accuracy of developed method was checked after addition/recovery tests. Recoveries and RSD (n = 12) for all elements varied within the 78–114% and 0.4–2% ranges, respectively. Limits of detection for all elements obtained by combining CRI and ICP-QMS were always better than 0.80 µg L−1 except for Si at 14 µg L−1.

Experimental characterization of the effect of skimmer cone design on shock formation and ion transmission efficiency in the vacuum interface of an inductively coupled plasma mass spectrometer

Laser-induced fluorescence has been used to evaluate five commercially available skimmer cone designs from inductively coupled plasma mass spectrometers in terms of shock formation at the skimmer tip and transmission efficiency. Efficiency was measured as the ratio of analyte density downstream from the skimmer tip to analyte density upstream from the skimmer tip. The strongest shock was recorded for a skimmer with a cylindrical throat, and the weakest shock was produced by the skimmer with the largest diameter and a conical throat. Transmission efficiency increased with increasing orifice diameter. Coulombic effects, revealed in a comparison between the behaviors of neutral barium atoms and barium ions, were small. Transmission efficiencies recorded for calcium ions were lower than those recorded for barium ions by more than a factor of two.

Improved in situ Hf isotope ratio analysis of zircon using newly designed X skimmer cone and jet sample cone in combination with the addition of nitrogen by laser ablation multiple collector ICP-MS

The effect of three different cone combinations on the performance of laser ablation MC-ICP-MS (Neptune plus) for the in situ Hf isotope analysis of zircon were investigated. The signal sensitivities of Hf, Yb and Lu were improved by a factor of 1.4 and 2.5, respectively, with using the X skimmer cone + standard sampler cone and the X skimmer cone + Jet sample cone compared to the standard arrangement (H skimmer cone + standard sample cone). However, when using the high-sensitivity Jet sample cone, the instrumental mass fractionation for hafnium displayed a large non-linear component that could not be corrected using the normal mass fractionation laws. The magnitude of this non-linear mass fractionation was strongly related to the central gas flow rate. The in situ Hf isotope analysis of zircon standards 91500 and Mud Tank using the Jet cone displayed large deviations (410–470 ppm) at the optimum central gas flow rate for Hf, which seriously deteriorated the performance of the Jet cone. The addition of 4 ml min−1 nitrogen to the central gas flow in laser ablation MC-ICP-MS was found to not only increase the sensitivity of Hf by a factor of 2.1, but also suppress this non-linear mass fractionation. The determined Yb/Hf and Lu/Hf ratios at their corresponding optimum makeup gas flow rates for Hf intensity were found to be reduced by factors of 2 and 1.3 in the presence of nitrogen, respectively, which would benefit the accurate in situ determination of Hf isotopes in high-content Yb and Lu samples. Compared to the standard arrangement, the corresponding precision (2σ) of 176Hf/177Hf for single spot analysis of zircon standard 91500 was improved from 224 ppm to 50 ppm by using the newly designed X-skimmer cone and Jet sample cone in combination with the nitrogen addition technique. The determined 176Hf/177Hf ratios are in excellent agreement with published values in five reference zircon standards (91500, GJ-1, Mud Tank, Penglai and Plesovice). Our first Hf isotopic results from zircon standard M257 (0.281544 ± 0.000018; 2SD, n = 151) showed that it was fairly homogeneous in Hf isotopes. These results clearly demonstrate that the present analytical method has the potential to become an important tool for the pursuit of high-quality in situ Hf isotope data for zircons.

Optimisation of whole blood and plasma manganese assay by ICP-MS without use of a collision cell

Manganese (Mn) toxicity has been reported in patients receiving total parenteral nutrition. To avoid unnecessary exposure it is recommended by NICE (National Institute for Clinical Excellence) that blood Mn concentrations are monitored. The aim of the study was to develop a method using inductively coupled plasma mass spectrometry (ICP-MS) for the reliable determination of Mn in plasma and whole blood, as indices of acute and chronic exposure. Whole blood and plasma samples were prepared by appropriate dilution (diluent containing 0.005% Triton X-100, 0.2% propan-2-ol, 0.2% butan-1-ol and 1% nitric acid) addition of an internal standard gallium, followed by centrifugation to remove cell debris. Thermo Fisher Scientific ExCell and X Series ICP-MS instruments were used to define and correct for polyatomic interference on Mn assay. Mn was quantified at mass 55 using aqueous calibration and the polyatomic interference from FeH was successfully eliminated by modified (Xt) skimmer cones but not with the collision cell (collision gas 7% H2 in He, flow rate 4-7 mL/min). The assay was validated showing good precision, limit of detection and percentage recovery. Good agreement was observed with the All Laboratory Trimmed Mean of External Quality Assurance samples y (in house)=1.1 (ALTM)-45.0 between values of 250 and 750 nmol/L. A method has been developed using ICP-MS for the analysis of whole blood and plasma Mn incorporating a novel method of eliminating interference by utilizing the different geometries of the Xt interface cones. The procedure is simple and robust with good precision and recovery over a wide dynamic range.

Performance evaluation of collision–reaction interface and internal standardization in quadrupole ICP-MS measurements

The combined use of internal standardization with collision and reaction interface in an inductively coupled plasma quadrupole mass spectrometer (ICP-QMS-CRI) was evaluated. The behavior of several elements (Ba, Cd, Co, Cr, Cu, Li, Mn, Mo, Pb, Sb, V and Zn) was studied by introducing H2 or He through the skimmer and sampler cones of the CRI device and by using In, Rh and Sc as internal standards. Certified reference material of trace elements in water (NIST 1643e) was used to evaluate the performance of the method. A vinegar sample and mixed food diet standard reference material were directly introduced into the equipment as complex matrices for Cr and V determinations. Improvements in accuracy and precision were attained combining both strategies. The introduction of H2 through the skimmer cone was the best way to overcome polyatomic ions formation and to improve SBR and BEC values for several elements. The use of Sc as internal standard improved the performance of ICP-QMS-CRI.

Combination of cool plasma and collision-reaction interface for correction of polyatomic interferences on copper signals in inductively coupled plasma quadrupole mass spectrometry

Inductively coupled plasma mass spectrometry (ICP-MS) is an important instrumental technique for elemental analysis. However, some elements suffer from spectral interferences caused by ions derived from argon plasma gas and matrix components. The determination of copper isotopes is affected by 40Ar 23Na + and 40Ar 25Mg +. The performance of an ICP-MS with a collision reaction interface (CRI) and cool plasma conditions for correction of spectral interferences was evaluated here. The efficiency of the CRI was studied introducing H 2 or He through sampler and skimmer cones. Gas introduction through the sampler cone was ineffective. Complete elimination of spectral interferences was reached when introducing 60 or 80 mL min −1 of H 2 in the skimmer cone, but sensitivity losses were as large as 99%. Further, the effect of interferences was checked when the argon plasma was operated under cool plasma conditions. The effects of the applied radiofrequency (0.6, 0.8, 0.9, and 1.0 kW), sampling depth (5.5, 8.5 and 11.5 mm), and dwell time (25 and 50 ms) were studied considering interference reduction and sensitivities. Best conditions were reached at 0.8 kW. Subsequently, both CRI and cool plasma conditions were combined to evaluate their performance on reduction of polyatomic Na and Mg argide interferences. Spectral interferences were eliminated using a CRI with 20 mL min −1 H 2 introduced through the skimmer cone, cool plasma conditions at 0.8 kW and sampling depth of 8.5 mm. This work demonstrated the feasibility of combining CRI and cool plasma for circumventing some spectral interferences on Cu determination by ICP-QMS.

Sensitivity improvement in laser ablation inductively coupled plasma mass spectrometry achieved using a methane/argon and methanol/water/argon mixed gas plasma

The influence of the addition of carbon using methane or methanol/water to an inductively coupled plasma (ICP) via the carrier gas flow on the sensitivity in laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was studied. During the ablation of SRM NIST 610 with simultaneous addition of CH(4) (0.6-1.4 ml min(-1)), a sensitivity enhancement of more than one order of magnitude for selected analytes (e.g. (75)As(+)) was observed. In addition to the sensitivity enhancement for As, Te, I and Se, also all other measured elements showed a significantly enhanced sensitivity (minimum by a factor of 2). Potential mechanisms for the observed intensity enhancement include charge transfer reactions, a change in the ICP shape and a temperature increase in the plasma. Furthermore, the aspiration of a methanol-water mixture into a cooled spray chamber and the simultaneous addition to the laser ablated aerosol was investigated. This type of mixing leads to a sensitivity enhancement up to a factor of 20. To prevent clogging of the sampler cone and skimmer cone by carbon deposition, a fast cleaning procedure for the interface is tested during running ICP, which allows the application of such a set-up for specific applications.

Slurry Nebulization-Inductively Coupled Plasma Mass Spectrometry with Solution Calibration for Determination of Ultratrace Boron in High Pure Nuclear Graphite Powder

The method of slurry nebulization-inductively coupled plasma mass spectrometry ( SN-ICP-MS) was developed for the direct determination of trace boron in high purity graphite powders. The particle size was controlled <5 mu m after the graphite powders was ground and sifted. Polyvinylpyrrolidone (PVP) was used as the dispersant in slurry preparation. The optimal mass ratio of PVP to the graphite was found to be 0.5. Well proportioned and stable slurry solution was obtained by magnetic stirrer. About 0.1 mol/L NH4OH as the aqueous medium could provide the optimal pH of 10 for the stable slurry and eliminate the memory effect of B. ICP-MS was operated in a higher resolution mode (0.6 amu) to eliminate the interference with the matrix C-12 by peak tailing. Oxygen was added into the plasma at a flow rate of 60 mL/min, to resolve carbon deposition on the sampler and skimmer cones and accelerate particle dissociation in the plasma. External calibration with aqueous solution standards was established for quantification. Beryllium was chosen as the internal standard to evaluate the efficiency of matrix effect correction. A correlation coefficient of 0.9995 for boron concentrations from 2 to 200 mu g/L was obtained with a detection limit (3s) of 0.095 mu g/g. As a practical application, with the advantage of simple, quick and low losing, the proposed method was applied to determine the trace boron in four nuclear graphite samples ( claimed 99.999% purity), with the satisfactory recoveries for the spike tests in the range of 97.2% - 103.1%.

Bonding Stability and Dehydration Constants for Hydrated Metal Ions

The bonding of water molecules with univalent metal ions (M+) has been studied by electrospray ionization mass spectrometry (ESI-MS). Increasing the voltage between the skimmer cones (referred to as the cone voltage) induced the abstraction of water molecules from M+(H2O)n ions, for n equal to 1 or 2. The ions studied belonged to the alkali metals (M = H, Li, Na, K, Rb, and Cs) and to the copper family (M = Cu and Ag). The energies of water binding with the cations studied change in a different manner for alkali metal cations than for the Ag+, Cu+, and H+ ions. A new method has been presented to determine the bonding stability and the dehydration constants for M+(H2O)n clusters.

Behaviour of arsenic and selenium in an ICP-QMS with collision and reaction interface

The performance of a collision reaction interface (CRI) for minimization of spectral interferences on analytical signals of 75As+ and 76Se+, 77Se+, 78Se+, 80Se+ and 82Se+ isotopes was evaluated by using H2 and He gases introduced through the sampler or skimmer cones of an inductively coupled plasma quadrupole mass spectrometer (ICP-QMS). Different gas flow rates were tested employing reference solutions prepared either in hydrochloric acid or in water soluble tertiary amines (CFA-C) media as carbon source. A hydrogen gas flow rate at 60 mL min−1 introduced through skimmer cone was effective for minimizing polyatomic interferences on 75As+ and Se isotopes, except for 80Se+. The use of He introduced through sampler or skimmer cones had a minor effect on the minimization of interferences when compared to the use of H2 gas. Moreover, it was observed that the gas introduction through the sampler cone had no effect on interferences when using gas flow rates up to 80 mL min−1 for both gases evaluated. Based on these results, it can be recommended to use H2 gas introduced through skimmer cone of the CRI for correcting polyatomic interferences on 75As+ and Se isotopes in matrixes containing up to 2% v v−1 chloride.

Lithium isotope analysis of natural and synthetic glass by laser ablation MC-ICP-MS

This contribution presents the first laser ablation multicollector ICP-MS (LA-MC-ICP-MS) technique for the measurement of Li isotopes. A Nu Instruments NuPlasma HR operating at 6 kV and fitted with a non-standard “low-mass, high abundance” skimmer cone is used, coupled to a NewWave UP213 213 nm laser ablation unit operating under a He atmosphere. Asymmetric tuning of the quad lenses on the NuPlasma allows the simultaneous measurement of 7Li and 6Li on a Faraday-ion counter configuration. Use of the standard-bracketing technique for analysis of unknowns obviates any cross calibration between Faraday cup and ion counter. Use of a natural glass as bracketing standard (e.g. BCR-2G) yields accurate Li isotope data with external, measured 2σ δ7Li precision of <1‰ at Li concentrations of 3–35 ppm.

A comparison between HPLC-dynamic reaction cell-ICP-MS and HPLC-sector field-ICP-MS for the detection of glutathione-trapped reactive drug metabolites using clozapine as a model compound

In this study, a novel method was developed for tracing down reactive drug metabolites, the formation of which in the human body constitutes an important health risk as a result of their capability to bind to body proteins and DNA. Clozapine was used as a model because this drug forms both reactive and stable metabolites. Glutathione, which forms complexes with reactive metabolites, was added in order to trap reactive species of clozapine, formed by degradation in an electrochemical cell, thereby mimicking the real drug metabolism process. The method developed is based on the use of reversed-phase HPLC as a chromatographic separation technique and inductively coupled plasma-mass spectrometry (ICP-MS) for monitoring of Cl and S. Via Cl-monitoring, all metabolites of the Cl-containing clozapine can be detected, whereas S-monitoring allows for the detection of the S-containing molecule glutathione and its conjugates with reactive metabolites. The spectral overlap of the signals of 32S+ and 34S+ with those of 16O16O+ and 16O18O+, respectively, was tackled in 2 ways. On one hand, a quadrupole-based ICP-MS instrument, equipped with a dynamic reaction cell, was used. O2 was used as a reaction gas to convert the S+ ions to a sufficient extent into the corresponding SO+ species. This did not yield optimal results, due to pronounced ArC+ signals at mass 48 and 50 upon introduction of methanol into the ICP. On the other hand, a sector-field ICP-MS instrument operated at medium mass resolution permitted interference-free monitoring of the S+-signals. A new type of skimmer cone – termed X-skimmer – was evaluated and its use resulted in a 4-fold increase in the sensitivity in a methanolic environment, providing a limit of detection of 1 μg L−1 for S. The chromatograms obtained via HPLC-SF-ICP-MS permitted differentiation between reactive and stable metabolites. As a result, the method developed looks very promising for the detection of glutathione conjugates and shows potential for their quantification in early stages of drug development when a radiolabeled compound is not yet available.

Water Molecule Coupling to MeCl+ and MeClO4 + Ions Studied by the Electrospray Ionisation Mass Spectrometry

Abstract The binding stability of water molecules with MeCl+ and MeClO4 + ions has been studied by the electrospray ionisation mass spectrometry (ESI-MS). The Me ions studied were the typical transition metals (Me = Fe, Co, Ni, Cu, Zn, or Cd) and the typical alkaline-earth metals (Me = Mg, Ca, Sr, or Ba). The increasing voltage between the skimmer cones (referred to as the cone voltage) induced the abstraction of water molecules from MeCl+ and MeClO4 + ions. The binding stability of water molecules with MeCl+ and MeClO4 + ions has been correlated with the Me cation mass and with the heat capacity of hydration of Me cations. Moreover, the physicochemical properties of the ions studied have been compared by the cluster analysis and the principal component analysis of the experimental curves obtained for the [MeCl-H2O]+ and [MeClO4-nH2O]+ ions, where n is 1 or 2. Our results can be useful in examination of the ion dehydration process.