Results of an interlaboratory comparison for characterization of Pt nanoparticles using single-particle ICP-TOFMS

This study describes an interlaboratory comparison (ILC) among nine (9) laboratories to evaluate and validate the standard operation procedure (SOP) for single-particle (sp) ICP-TOFMS developed within the context of the Horizon 2020 project ACEnano. The ILC was based on the characterization of two different Pt nanoparticle (NP) suspensions in terms of particle mass, particle number concentration, and isotopic composition. The two Pt NP suspensions were measured using icpTOF instruments (TOFWERK AG, Switzerland). Two Pt NP samples were characterized and mass equivalent spherical sizes (MESSs) of 40.4 ± 7 nm and 58.8 ± 8 nm were obtained, respectively. MESSs showed <16% relative standard deviation (RSD) among all participating labs and <4% RSD after exclusion of the two outliers. A good agreement was achieved between the different participating laboratories regarding particle mass, but the particle number concentration results were more scattered, with <53% RSD among all laboratories, which is consistent with results from previous ILC studies conducted using ICP-MS instrumentation equipped with a sequential mass spectrometer. Additionally, the capabilities of sp-ICP-TOFMS to determine masses on a particle basis are discussed with respect to the potential for particle density determination. Finally, because quasi-simultaneous multi-isotope and multi-element determinations are a strength of ICP-TOFMS instrumentation, the precision and trueness of isotope ratio determinations were assessed. The average of 1000 measured particles yielded a precision of below ±1% for intensity ratios of the most abundant Pt isotopes, i.e.194Pt and 195Pt, while the accuracy of isotope ratios with the lower abundant isotopes was limited by counting statistics

ICP-MS for the analysis at the nanoscale – a tutorial review

This tutorial review focuses on the use of ICP-MS based techniques for the analysis of metal-containing nanoparticles and colloids. Within the first part the capabilities of “stand alone” ICP-MS for the analysis of total metal contents and the suitability of stable isotopes for nanoparticle tracking (stable isotope labelling and naturally occurring variation in isotope ratios) are introduced (Chapter 3). Special focus was given on single particle ICP-MS (sp-ICP-MS) mode (Chapter 4). Upon a brief introduction into the theoretical concept, critical aspects such as calibration strategies, dwell time as well as ionic background were discussed and practical advice is given. References to current data assessment sheets are provided. Furthermore, a brief chapter on general sample preparation aspects is included within the first part (Chapter 2). The second part is dedicated to fractionation/separation systems, such as field-flow fractionation (FFF), hydrodynamic chromatography (HDC), high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) coupled on-line with ICP-MS detection for metal-based nanoparticle and colloid analysis (Chapter 5). Each section starts with an introduction into the theoretical concept of the respective fractionation/separation system, followed by practical hints regarding method development (e.g. selection of appropriate carrier/mobile phase, membrane/stationary phase) as well as critical aspects and limitations. Particular attention is payed to laser ablation ICP-MS (LA-ICP-MS) for spatially resolved nanoparticle analysis. Each section concludes with selected application examples of the respective analytical technique from the most relevant fields of nanoparticle use or exposure (consumer products, food, medicine and environment), highlighting the performance of each technique in metal-based nanoparticle analysis. Chapter 6 is dedicated to aspects of quality assurance. Various critical points regarding method development and validation, mass balance, size calibration and quantification from the previous sections are revisited, discussed and practical advice is given. Finally, the authors provide some concluding remarks and future perspectives (Chapter 7). Furthermore, a flow-chart is included as a “hands-on” overview on all ICP-MS based techniques discussed within this tutorial review intended as a “method-decision tool” for users

Method development for on-line species-specific sulfur isotopic analysis by means of capillary electrophoresis/multicollector ICP-mass spectrometry

In this work, a method for species-specific isotopic analysis of sulfur via capillary electrophoresis hyphenated on-line with multicollector ICP-MS (CE/MC-ICP-MS) was developed. Correction for the mass bias caused by instrumental mass discrimination was realized via external correction with multiple-injection sample-standard bracketing. By comparing the isotope ratio measurement results obtained using the newly developed on-line CE/MC-ICP-MS method with those obtained via traditional MC-ICP-MS measurement after analyte/matrix separation by anion exchange chromatography for isotopic reference materials and an in-house bracketing standard, the most suitable data evaluation method could be identified. The repeatability for the sulfate-delta S-34 value (calculated from 18 measurements of a standard conducted over seven measurement sessions) was 0.57 parts per thousand (2SD) and thereby only twice that obtained with off-line measurements (0.30 parts per thousand,n = 68). As a proof of concept for analysis of samples with a real matrix, the determination of the sulfur isotopic composition of naturally present sulfate was performed for different river systems. The CE/MC-ICP-MS results thus obtained agreed with the corresponding off-line MC-ICP-MS results within the 2SD ranges, and the repeatability of consecutive delta S-34 measurements (n = 3) was between 0.3 parts per thousand and 1.3 parts per thousand (2SD). Finally, the isotopic analysis of two different S-species in a river water sample spiked with 2-pyridinesulfonic acid (PSA) was also accomplished

Application of stable isotopes and AF4/ICP-SFMS for simultaneous tracing and quantification of iron oxide nanoparticles in a sediment–slurry matrix

One major challenge in nanomaterial analysis, especially in complex environmental matrices, is the unambiguous differentiation between natural and engineered nanomaterials (ENMs). Particularly with regard to the investigation of ENM's/engineered nanoparticle's (ENPs) fate, analytical methods are needed allowing for tracing and sensitive quantification. Several ENPs are metal-based and contain elements being omnipresent in environmental matrices (e.g., Al, Ti, Zn, Fe and non-metal Si) - hence, high background levels of these elements are expected, compromising sensitive detection. In this work we developed successfully a combined approach of stable isotope labeling (tracing) and reverse postchannel species-unspecific on-line isotope dilution (quantification) in combination with AF4/sector-field ICP-MS (AF4/ICP-SFMS). The approach was successfully applied to iron oxide nanoparticles isotopically enriched in Fe-57 coated with a SiO2 shell (Fe-57@SiO2 ENPs). Upon method development and validation the Fe-57@SiO2 ENPs were spiked into a filtered re-suspended river sediment-slurry matrix for proof-of-concept. Our approach allowed for unambiguous tracing of the Fe-57@SiO2 ENPs among natural iron colloid fractions as well as simultaneous sensitive quantification via reverse on-line ID despite high "natural" iron background. A limit of detection of 2.4 mu g Fe L-1 and a limit of quantification of 7.8 mu g Fe L-1 in real matrix was achieved. Furthermore, a good reproducibility in terms of peak areas was obtained (0.4-3.0%); the RSDs for elution times vary between 0.1 and 0.7%. To the best of the authors' knowledge, for the first time a reverse post-channel on-line isotope dilution AF4/ICP-SFMS approach in combination with isotopically labeled Fe-57@SiO2 ENPs was developed, allowing for (i) unambiguous tracing, and simultaneous (ii) sensitive quantification of the Fe-57@SiO2 ENPs within a sediment slurry matrix in the presence of natural iron colloid fractions. Based on the experience gained in this work, we feel certain that the approach is deployable to further stable isotope labeled metal-and nonmetal-based ENMs and shows great potential in ENMs studies

Fraction-related quantification of silver nanoparticles via on-line species-unspecific post-channel isotope dilution in combination with asymmetric flow-field-flow fractionation (AF4)/sector field ICP-mass spectrometry (ICP-SF-MS)

Engineered nanoparticles (ENPs) show new and interesting properties leading to an increased use in various application fields and have entered our daily environment (e. g., functionalized clothing, cosmetics, food, medicine). Though on the one hand nanotechnology plays a substantial role in societies' daily life, on the other the presence and behavior of ENPs in organisms and the environment is still unclear to a large extent. Furthermore, comprehensive legislative regulation is still missing. For adequate regulation a clear definition of ENPs is needed. A definition recommendation was released in 2011 by the European Commission (EC) on the basis of size and number of ENPs present within a defined size range. However, straightforward analytical techniques which easily provide information allowing for a decision (based on the EC definition) on the presence and concentration of ENPs in a given sample do not exist yet. A promising tool, offering fraction-related size information on the one hand and allowing for element-specific detection on the other is the coupling of asymmetric flow-field-flow-fractionation (AF4) with inductively coupled plasma-mass spectrometry (ICP-MS). In this work, a new strategy for quantifying silver nanoparticle (AgNP) size fractions (30 nm +/- 2.1 nm, 75 nm +/- 3.9 nm) after base-line AF4 separation relying on on-line ICP-MS detection combined with "post-channel" species-unspecific online isotope dilution (on-line ID) was successfully developed. A limit of detection (LOD) of 0.5 mu g Ag L-1 and a limit of quantification (LOQ) of 1.6 mu g Ag L-1 were achieved by the approach applied. The recovery values for the smaller size-fraction (30 nm) were in the range of 31-41% while for the larger size-fraction (75 nm) in the range of 75-78%. The overall reproducibility (RSDs, peak areas) was in between 3.4-5.4%. Validation of the on-line ID approach was achieved via off-line fraction collection and total silver determination afterwards; a bias of 2.9-16.4% between both approaches was observed indicating that the on-line ID approach is working properly. To the best of the authors' knowledge, this is the first time that species-unspecific (post-channel) on-line ID was combined with AF4/ICP-SF-MS for fraction-related quantification of AgNPs

Speciation analysis of bromine-containing drug metabolites in feces samples from a human in vivo study by means of HPLC/ICP-MS combined with on-line isotope dilution

The aim of this work was speciation analysis of metabolites in feces samples collected within a clinical study during which a bromine-containing anti-tuberculosis drug (TMC207) was administered to patients with multi-drug resistant tuberculosis infection. Owing to slow elimination of the drug, no (14)C label was used within this study. Quantification of the bromine species was accomplished using high performance liquid chromatography coupled to inductively coupled plasma-mass spectrometry (HPLC/ICP-MS) in combination with on-line isotope dilution (on-line ID), while structural elucidation of the species was performed using HPLC coupled to electrospray ionization-mass spectrometry. The ICP-MS-based method developed shows a good intra- and inter-day reproducibility (relative standard deviation = 3.5%, N = 9); the limit of detection (1.5 mg TMC207 L(-1)) is of the same order of magnitude as that for HPLC/radiodetection; the dynamic range of the method covers more than two orders of magnitude. Furthermore, the column recovery was demonstrated to be quantitative (recoveries between 90.6% and 99.5%). Based on the excellent figures of merit, the "cold" HPLC/ICP-MS approach could be deployed for the actual human in vivo metabolism study, such that exposure of the human volunteers to the (14)C radiolabel was avoided

HPLC/ICP-MS in combination with 'reverse' online isotope dilution in drug metabolism studies

During the development of a new drug compound, its metabolism needs to be unraveled. For quantification of the metabolites formed, the drug under investigation is traditionally synthesized with a radiolabel (C-14 or H-3) and the metabolites present in different matrixes (blood, urine, feces) upon drug administration are determined by means of high-performance liquid chromatography (HPLC) coupled to radiodetection. This approach allows for quantification of the metabolites formed and enables a straightforward distinction between exogenous (i.e., drug-related) and endogenous species (as only the radiolabeled species are detected). However, in some cases, the use of a radiolabeled compound in human in vivo studies is not advisible, e.g., for drug compounds or their metabolites showing a long plasma or tissue half-life. In cases where the candidate drug molecule contains an element detectable by means of inductively coupled plasma mass spectrometry (ICP-MS), HPLC/ICP-MS is a promising alternative approach. However, the method lacks specificity when a distinction between drug-related species and endogenous compounds containing the same target element needs to be accomplished. As a result, we have developed an HPLC/ICP-MS-based method combined with "reverse" online isotope dilution ("reverse" online ID) for metabolite quantification. The methodology was evaluated by the analysis of feces samples from rats dosed with a Br-81-labeled drug compound. The method allows for both (i) valid quantification of the drug metabolites and (ii) distinction among endogenous, exogenous, and "mixed" species, based on their isotopic "fingerprint". A good repeatability (relative standard deviation of 4.2%) and limit of detection (0.35 mg of drug compound L-1 of feces extract), of the same order of magnitude as those observed for "normal" online ID HPLC/ICP-MS and HPLC/radiodetection, were achieved

Ingestion and toxicity of microplastics in the freshwater gastropod Lymnaea stagnalis: no microplastic-induced effects alone or in combination with copper

The interaction of microplastics with freshwater biota and their interaction with other stressors is still not very well understood. Therefore, we investigated the ingestion, excretion and toxicity of microplastics in the freshwater gastropod Lymnaea stagnalis. MP ingestion was analyzed as tissues levels in L. stagnalis after 6–96 h of exposure to 5–90 μm spherical polystyrene (PS) microplastics. To understand the excretion, tissue levels were determined after 24 h of exposure followed by a 12 h–7 d depuration period. To assess the toxicity, snails were exposed for 28 d to irregular PS microplastics (<63 μm, 6.4–100,000 particles mL−1), both alone and in combination with copper as additional stressor. To compare the toxicity of natural and synthetic particles, we also included diatomite particles. Microplastics ingestion and excretion significantly depended on the particle size and the exposure/depuration duration. An exposure to irregular PS had no effect on survival, reproduction, energy reserves and oxidative stress. However, we observed slight effects on immune cell phagocytosis. Exposure to microplastics did not exacerbate the reproductive toxicity of copper. In addition, there was no pronounced difference between the effects of microplastics and diatomite. The tolerance towards microplastics may originate from an adaptation of L. stagnalis to particle-rich environments or a general stress resilience. In conclusion, despite high uptake rates, PS fragments do not appear to be a relevant stressor for stress tolerant freshwater gastropods considering current environmental levels of microplastics