Atomic Spectrometry Update: review of advances in the analysis of clinical and biological materials, foods and beverages
Andrew
Taylor
*a,
Nicola
Barlow
b,
Martin P.
Day
c,
Sarah
Hill
d,
Nicholas
Martin
e and
Marina
Patriarca
f
aGuildford, Surrey, UK. E-mail: m220501@aol.com
bTrace Elements Laboratory, Department of Clinical Biochemistry, Sandwell General Hospital, West Bromwich, West Midlands B71 4HJ, UK
cThe Australian Wine Research Institute, PO Box 197, Glen Osmond, SA 5064, Australia
dLGC, Queens Road, Teddington, Middlesex TW11 0LY, UK
eDepartment of Clinical Biochemistry, Charing Cross Hospital, 8th Floor Lab Block, Fulham Palace Road, London, W6 8RF, UK
fIstituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy
First published on 31st January 2019
Abstract
This Update covers publications from the second half of 2017 to the middle of 2018. Techniques and applications relevant to clinical and biological materials, foods and beverages are discussed in the text, presenting key aspects of the work referenced, while the tables provide a summary of the publications considered. Original approaches to sample extraction reported include using deep eutectic solvents, protonated triethylamine carbonate which converts to the immiscible triethylamine by addition of NaOH, a switchable hydrophilic solvent and new solid phase materials. The ingenuity of analytical scientists is illustrated by the development of an apparatus for sequential determination of Cd and Hg in foods by VG-AFS. Different parts of the equipment perform sample destruction, separation of Cd from Hg, vaporisation, trapping, volatilisation and measurement. Other new devices include a microwave plasma torch linear ion trap mass spectrometer suitable for field analysis of water and tandem LA-LIBS with ICP-MS. Various applications with single particle or single cell ICP-MS, particularly associated with nanoparticles, follow from work we have included in our recent Updates. Growing interest in clinical exposure to Gd is noted while work relating to Cu metabolism in Wilson’s disease provides new information for a disorder that has already been studied for many decades. Following from new food safety regulations, concentrations of Cd in cocoa are being investigated. Higher concentrations are seen in S American products although, having been consumed for centuries, whether or not there is any harm seems questionable. Encouraging for those who enjoy caviar is a study suggesting that samples from the polluted Caspian Sea may not contain high concentrations of toxic elements.
1 Reviews
This latest Update adds to that from last year1 and complements other reviews of analytical techniques in the series of Atomic Spectrometry Updates, also from the previous year.2–7An eclectic series of interesting review articles feature among publications during the last year. Referring to determining the content and distribution of trace elements on the surface of clinical materials by LA-ICP-MS, Sajnog et al.8 considered the metrological aspects associated with sampling, preparation and analysis. Much of this is probably taken for granted by analysts, as factors such as traceability of calibrators, assay validation parameters and uncertainty of measurements are rarely included in published work. Two reviews discussed developments around identification of metals in biological samples relevant to the structure and function of cells and tissues. Busser et al.9 described the advantages of LIBS for elemental detection, quantification and imaging. Examples involving human, animal and vegetable specimens were presented. Among the advantages cited, the authors mentioned minimal sample preparation, simultaneous detection of low- and high-atomic-number elements and compatibility with optical microscopy. Wang et al.10 reviewed the performance of new ICP-MS-based procedures and their application to species analysis within cells. Reference was made to chip-based microextraction techniques and separations by multi-dimensional chromatography and electrophoresis. Analyses from single cells was noted, particularly when LA was used for sample introduction. The implications of these techniques for clinical applications and research were presented. Bizzi and colleagues11 also refer to recent developments in atomic spectrometric techniques and how these have extended the possibilities for multi-elemental analyses at trace levels in a variety of matrices. Highlighting that results can be influenced by matrix-related effects causing spectral and non-spectral interferences, the authors go on to review developments to improve digestion procedures, particularly those that avoid concentrated acids. These included the use of dilute acid solutions with the aid of O2, H2O2 and UV-assisted digestion, high pressure flow digestion, and combustion methods, all assisted by microwave radiation. Further to work reported in our recent ASUs, Hernandez-Hernandez et al.12 reviewed use of magnetic nanoparticles as sorbents in dispersive solid-phase microextraction for the analysis of food samples. The main advantage of these materials was given as the ease of separation from the food matrix with the aid of a magnet leading to rapid preparation, low cost, high concentration factors, and low detection limits. Hu et al.13 discussed how single-particle ICP-MS (spICP-MS) may be applied to metallic nanoparticle tagged bioassays reviewing the range of metallic nanoparticles currently available and how the simultaneous multiplex detection capability of ICP-TOF-MS can be exploited.
Articles referring to elemental hair analysis published in the last 10 years were evaluated by Pozebon et al.14 yet the content and conclusions are remarkably similar to those in a review from 1986 (Ann. Clin. Biochem., 1986, 23, 364–378).
2 Metrology, interlaboratory studies, reference materials and reference ranges
The most striking achievement in metrology during the past year was without doubt the resolution, to redefine four units of the International System of Units (SI), including the mole. This was agreed unanimously at the 26th meeting of the General Conference on Weights and Measures (http://www.bipm.org), in November 2018, and received significant media attention. With the new definitions of units for the quantities mass, amount of substance, thermodynamic temperature and electric current, all SI units are now linked to fundamental constants of physics and other constants of nature, whose values were determined with improved accuracy and uncertainties due to the work carried out in several international research projects since 2011. The last physical artefact of the SI, the “kilogram”, carefully kept under three glass bells at the International Bureau of Weights and Measures (Paris, France) will soon be archived. The mole will be linked directly to the value of the Avogadro constant, determined experimentally as 6.02214076 × 1023 mol−1. The decision, effective from the 20th of May 2019 (“World Metrology Day”), fulfils the essential requirements of long-term stability and internal self-consistency of the SI, as well as promoting its world-wide accessibility. Although virtually no change will be seen by analysts in the short term, this achievement opens the way to future developments in all areas of measurements and especially where new technologies are applied.In this year’s review, no reports of substantial advancements in the area of development of reference materials were published. Pacquette and Thompson15 provided the results of an inter-laboratory study to evaluate the repeatability and reproducibility of a candidate standard method for milk and milk products (ISO/DIS 21424). Ten laboratories, using five different ICP-MS models, determined the mass fractions of 12 elements (Ca, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, P, Se and Zn) in 50 blind duplicate samples including milk, milk powder, whey powder, butter and cheese, infant and nutritional formulas and a SRM, after microwave-assisted digestion. The typical sample size for liquid products was 1 g diluted to a final volume of 50 mL, whereas for powders, reconstituted as 25 g + 200 g water, 1.8 g of the slurry were diluted to the same final volume. The results were compared with those obtained on the same samples using ICP-OES.
Diet is the main source of exposure to potentially toxic elements for the general population in Europe and other industrialised countries. Besides the assessment of the content of chemical elements in individual food categories as part of national food control plans, the evaluation of the actual contribution of the diet to the exposure of population groups is influenced by the level of consumption of certain food types as well as losses or concentration of elements depending on food storage and preparation. Total diet studies are designed to address this issue, by considering the presence and the proportion of certain foods in the diet of specific population groups. Infants and toddlers are an important target group for these studies because of their vulnerability during growth and development. Their specific food requirements and higher absorption in comparison to adults.
In the first French study of this kind, Guerin et al.16 investigated the presence of Pb in the total diet of infants and toddlers. Following an established protocol, 291 food samples were selected on the basis of a survey on food consumption of children under 3 years of age. Twelve aliquots of each food item were collected during a year, then homogenised to obtain a composite sample. These were grouped into 36 food groups representing French children’s habits. Samples were wet-oxidised with 3 mL ultrapure water–3 mL concentrated HNO3 then diluted to a final volume of 50 mL with ultrapure water prior to analysis by ICP-MS. Improved LOQs of 0.6 μg kg−1 and 0.9 μg kg−1, for liquid and solid samples, respectively, were achieved. Food CRMs were analysed alongside the food samples. Measured levels of Pb ranged from less than the LOD to 16 μg kg−1 in most samples, with the highest Pb levels found in processed food products, especially foods containing chocolate. On average, infant food contained 2.2 μg kg−1 Pb, an estimate in agreement with data from the European Food Safety Authority, but lower than those reported in previous studies in Europe.
Following previously reported evidence that levels of Hg in human milk from Brazilian mothers was the highest in the world, a team of researchers, led by Caldas,17 investigated the risk of exposure to Hg species for lactating babies from the Federal District of Brazil, a region of low fish consumption. Sample preparation involved lyophilisation of a 5 mL milk aliquot and addition of 5 mL of 25% KOH in MeOH to 0.2 g of the lyophilized milk. The mixture was left at 70 °C for 6 h, then kept in the dark for 48 h. After centrifugation, ethylation was achieved by mixing 50 μL of the mixture with 50 μL of 1% tetraethylsodiumborate and 200 μL of 2 mol L−1 acetate buffer (pH 4.5), followed by dilution to 40 mL with ultrapure water. The mean weekly intake of MeHg was 0.16 ± 0.22 μg kg−1 b.w., as compared to the PTWI of 1.6 μg kg−1 b.w. established by FAO/WHO for foetuses and children, and in only one case, the intake exceeded the PTWI (1.90 μg kg−1 b.w.). The PTWI for iHg, set at 4 μg kg−1 b.w., was exceeded in 25 cases, all from the first 4 months of lactation, whereas the mean weekly intake was calculated as 2.1 ± 1.5 μg kg−1 b.w. The authors concluded that there was no appreciable risk of exposure to either MeHg or iHg for breastfed babies in this region of Brazil. The observed levels of total Hg were lower than those reported in previous studies in the same country.
In human biomonitoring studies, a careful statistical design is essential to ensure the measured levels and derived statistics are a fair representation of the population. With growing concern for the effects of environmental pollution on human health, following a trend already seen in last year's review,2 two papers reported information on biomonitoring studies performed in Korea. An extensive population-based cross-sectional study was carried out between 2010 and 2011 to determine the background levels of exposure to Cd, Hg and Pb. To obtain a representative sample of the Korean population, Park and coworkers18 designed a sampling method to address the geographical distribution of participants according to the country organisation structure – from regions to townships, for a total of 102 sampling sites. Within this framework, they recruited adults (aged 19 years or older), according to a sex- and age-stratified probability method, and preschool- and school-aged children, by a cluster sampling method, for a total of 4000 subjects (1886 men and 2114 women, aged from 0 to 83 years). Concentrations of Cd and Pb were measured in whole blood samples by ETAAS with Zeeman correction, after dilution with 0.2% Triton X-100–1% HNO3–0.2% (NH4)2HPO4, whereas Hg was determined in 100 mg of whole blood, by means of the gold-amalgam method, using a direct analyser. Detection limits of 0.10 μg L−1 (Cd), 0.20 μg L−1 (Hg) and 0.20 μg dL−1 (Pb) were achieved and the methods were validated by analysis of NIST SRM 955c, toxic metals in caprine blood. In only a small proportion of the blood samples (7 for Cd, 104 for Hg and 14 for Pb) were below the respective LODs. These samples were included in the statistics with assigned values equal to the LODs divided by the square root of two. The median and 95th percentile values respectively were: Cd 0.59 μg L−1 and 2.20 μg L−1; Hg 2.87 μg L−1 and 9.12 μg L−1; Pb 1.83 μg dL−1 and 3.78 μg dL−1. Significant sex related differences, reported in several other population studies, were confirmed for all three elements. Blood Cd was higher in women older than 30 years than in men of the same class of age, whereas men had higher Hg levels than in women, except in children and subjects of under 20 years of age. Men and boys had significantly higher blood Pb levels than women and girls, but no sex-related difference emerged for children aged from 0 to 4 years. As previously observed, blood metal levels generally increased with age. However, both Cd and Hg levels tended to decrease slightly in subjects above 59 years of age, whereas, for blood Pb, there was no strong evidence of an age trend between 0 and 19 years of age. Significant positive relationships were observed among the blood concentrations of Cd, Hg and Pb. The reported data provided a thorough assessment of the Cd, Hg and Pb exposure of the general population in Korea, also highlighting that Koreans had higher levels of blood Cd and Hg when compared with in the US, Canada and Germany. In future surveys, the inclusion of information regarding factors known to influence the levels of these elements in blood, for example occupation (Cd, Hg, Pb), smoking (Cd), consumption of fish and seafood (Hg) or rice (Cd), may help to address preventive actions.
In a study by Kim et al.,19 the levels of seven elements (Al, As, Cd, Cs, Hg, Mn and Pb) in blood and another three (Cu, Se, and Zn) in serum were determined by ICP-MS on a limited number of subjects enrolled from December 2014 to December 2016 at the Seoul Clinical Laboratories. After exclusion of individuals who had a disease, a medical history of a disease, or abnormal results in general chemistry and/or blood tests, 258 subjects (119 males and 139 females) were included in the study. The subjects’ age ranged from 12 to 78 years, but children (up to 19 years) and elderly (over 69 years) were underrepresented (9 samples in each category). The analytical procedure, for both whole blood and serum samples, involved a 10-fold dilution with sterile distilled water, followed by protein removal with 1% HNO3 (surprisingly 100 μL for blood vs. 200 μL for serum, despite the relevant difference in protein concentration) and addition of 10 μg L−1 Sc as the internal standard. Analyses were carried out on the supernatant, obtained after centrifugation at 3000 rpm for 15 min. Where possible, two isotopes of each element were measured. The median and 95th percentile values were reported for Al, As, Cd, Cs, Cu, Hg, Mn, Pb, Se and Zn. Analysis of gender-related differences generally confirmed previous findings of higher levels of As, Cs, Hg, Pb and Se in men, whereas Cd, Cu and Mn concentrations were higher in women. The influence of age on element concentrations was investigated by comparing those <50 years of age (n = 121) and those ≥50 years (n = 137), finding significant differences (p < 0.05) for the concentrations of As, Cd and Pb in blood, as observed in other studies. The levels of Pb in blood were still lower than in other areas of the world, and those for Cd and Hg were higher, confirming the results previously observed from a much larger population sample.18 The levels of Al, As and Cs were greater than in other parts of the world but not for Cu, Mn, Se or Zn. Unfortunately, no further information was available on specific factors (such as occupation, lifestyle or dietary habits), known to influence the concentration of some elements in body fluids.
Besides occupational exposure, smoking habits (Cd), use of oral contraceptives (Cu), consumption of fish and seafood (As, Hg) or rice (As, Cd) are some of the well known factors contributing to elevated blood or serum levels. In addition, different species of the target elements may have completely different toxicological profiles (see, for example, AB and MeHg, the major As and Hg species in fish and seafood, vs. AsIII, AsV and iHg) and, therefore, play a different role in the evaluation of health risks. In an attempt to address the complexity of factors implied in the evaluation of the environmental burden on health risk, Sarigiannis and his coworkers20 applied a so called “exposome approach” to design a human biomonitoring survey of the exposure to metals in adolescents. The study involved 453 subjects (242 girls and 211 boys), aged from 13 to 15 years, living in urban and rural areas of the Latium Region (Italy). Blood samples were analysed for 19 elements (As, Be, Cd, Co, Cr, Hg, Ir, Mn, Mo, Ni, Pb, Pd, Pt, Rh, Sb, Sn, TI, V, and W) by SF-ICP-MS after microwave-aided digestion of a 1 mL aliquot with ultrapure concentrated HNO3. Information on dental fillings and/or braces, current use of piercings and tattoos, second hand smoke exposure, frequency of fish and milk consumption, socio-economic status of the family was collected by means of a questionnaire. Data of air and water quality were supplied by the local EPA. Results below the LOD were assigned a value equal to half of the LOD and extreme values were excluded. Median and 95th percentile values were then calculated and were comparable with those reported in other recent studies in Europe, Canada and the US. Blood Ni and Pb were significantly (p < 0.05) higher in boys, whereas girls had higher concentrations of Hg in blood. The associations between biomarkers of internal exposure (concentrations in blood) and other variables collected during the study were further investigated by a number of techniques, using geo-statistical analyses based on a Geographical Information System, a Generalized Linear Model and the Environment-Wide Association Study methodology. The combination of such approaches, together with the information collected in well-designed biomonitoring studies, can identify associations among the different factors that contribute to possible health risks.
Hair has been considered as a potentially useful matrix for biomonitoring studies, in view of its accessibility and capability to provide data on the storage of elements in tissues, due to exposure over time and/or the nutritional status of the subjects. Several studies have investigated the matter, some with controversial conclusions, pointing out the effect of hair treatments, the importance of appropriate sample collection procedures, the influence of washing procedures and the large inter-individual variability, which all hamper the possibility to establish useful reference ranges. Between April 2008 and December 2009, Ballesteros et al.21 carried out a cross-sectional study, devoted to establish reference ranges for 18 elements in hair of children and adolescents. The enrolled subjects were 648 healthy children and adolescents (253 boys and 395 girls), from two locations in the city of Madrid (Spain) and one in a nearby village, aged from 0 to 18 years, whose hair had not been coloured or treated. A strand of hair of at least 0.5 cm of diameter was cut at 1–2 cm from the occipital position of the head using stainless steel scissors, previously rinsed in ultrapure water, and stored at room temperature in pre-washed polypropylene containers. Hair samples were washed with acetone and water, following an IAEA recommended procedure, then 10–20 mg of sample were digested in an oven at 80 °C for 16 h with 1 mL of Triton X-100 and 1 mL of concentrated HNO3, and made up to 1 g with ultrapure water prior to analysis by ICP-MS. The observed median levels were reported for Al, Ag, As, Ba, Bi, Cd, Cr, Co, Cu, Fe, Mn, Mo, Ni, Pb, Se, Sr, Tl and Zn. Girls had significant higher hair levels of Ag, Ba, Bi, Cd, Co, Cu, Mn and Sr, whereas the contrary was observed for Tl. A relationship was observed toward age as the independent variable for the concentrations of Ba, Se, Sr and Zn (positive) as well as for Ag, Al, As, Bi, Cd, Co, Cr, Fe, Mn, Mo, Ni, Pb and Tl (negative). The comparison between the results of this study and those of several others, carried out in Spain, Europe and other areas of the world, confirmed the large variability associated with elemental concentrations in hair, owing to conditions, such as geography, environmental pollution, life-style and dietary habits, which may hamper their use as biomarkers.
3 Sample collection and preparation
3.1 Collection, storage and preliminary preparation
In what, at first appears to be a macabre investigation, Amadasi et al.22 immersed pig bone samples in solutions at pH levels of 1 to 14, as well as, very acidic H2SO4 and very basic NaOH, for up to 70 days. Extracted solutions were analysed by ICP-OES, ICP-MS, FTIR EDXRF, XRPD and SEM. The rationale was to assist in the forensic identification of material from situations where corpses have been treated with highly acidic or basic liquids. Results suggested that human material may be identified within residual solutions especially with FTIR, ICP-OES, and EDXRF.3.2 Digestion, extraction and preconcentration
In a solid phase extraction procedure, glutaraldehyde cross-linked magnetic chitosan NPs were synthesised and used as an adsorbent for dispersive solid phase extraction of Pd from active pharmaceutical ingredients. The adsorbent was characterised by FTIR, XRD and TEM while FAAS was used to measure the Pd. The LOD was reported as 2.8 μg L−1 as and recoveries of spiked samples were from 91.7 to 97.6%.25 Arain et al.26 prepared a deep eutectic solvent from acetamide and ZnCl2 to extract Mn, as a complex with 1-(2-pyridylazo)-2-naphthol (PAN) at pH 4–11, from blood samples of patients suffering from different neurological disorders. The method was validated by analysis of NIST SRM 3132 Human Blood. An enhancement factor of 42 was obtained and the LOD was 0.29 μg L−1. An unusual LPME procedure was developed by Habibiyan et al.27 where protonated triethylamine carbonate added to the aqueous sample was converted to the immiscible triethylamine by addition of NaOH. Application of ultrasonic energy enhanced the formation of fine droplets and extraction of Cd, Co, Ni and Pb into the triethylamine phase. The analytes were measured using micro sample injection FAAS. Enhancement factors were in excess of 100 and the LODs were in the range of 0.24 to 0.76 μg L−1 with RSDs of 1.3 to 3.8%. Results from the analysis of a CRM confirmed the accuracy of the procedure which was then applied to a number of water, urine and tea infusion samples.
A simpler method was used by Kimura and colleagues28 to extract total organic halogens, used as disinfectant products to treat drinking water, from specimens of urine. Halogens in diluted samples were adsorbed onto activated carbon. Gases were released by pyrolysis and trapped in an aqueous solution. The total organic Br, Cl and I were separated by IC and determined by ICP-MS. Recoveries of spiked analytes were 78–99%. Mean concentrations of total organic halides in five urine samples from volunteers were, 82, 1850 and 21.0 μg L−1 as Br, Cl and I, respectively after drinking tap water, which were compared against those who consumed spring water, 88, 1090 and 10.3 μg L−1 as Br, Cl and I.
Incorporation of sustainable approaches into analytical sample preparation continues with use of ‘green’ solvents. An interesting approach developed by Habibiyan et al.,27 using a switchable hydrophilicity solvent to extract and concentrate Cd, Co, Ni and Pb from various aqueous samples is described in Section 3.2.1. An example of a deep eutectic solvent (DES) based on choline chloride, a green and simple-to-prepare version of ionic liquid, was used to extract Mn from green vegetables.30 Choline chloride (vitamin B4) was liquified by heating, then mixed with an organic acid (either citric, oxalic or tartaric) and heated for 2 h until viscous. Dried and ground green leafy vegetables were added to the DES (1.25 g L−1) and heated to 95 °C for 2 h. After centrifugation (4000 rpm, 2 min) the supernatant and washed solid residues were combined before Mn determination by ICP-OES. Although recoveries from the three DES solvents averaged 96%, and the LOQs varied slightly: 4.10, 1.13 and 1.68 μg L−1, respectively, the authors declined to make a categorical preference of organic acid. To mitigate the limited sensitivity of TXRF for the determination of heavy metals in water, Oskolok et al.31 used directly-suspended droplet LPME with molecular I2 to extract Hg. The sample (5 mL) was mixed with KI solution (0.7 mL, 0.001 mol L−1), H2SO4 (1.3 mL, 50%) plus C6H6 (50 μL) then stirred at 1250 rpm for <3 min. The suspended drop of C6H6 was extracted with a microsyringe, dispensed into a glass vial micro-insert and evaporated at 50 °C before redissolved in KI solution (0.01%, 70 μL) containing Ga IS (3 μg L−1). An aliquot of this solution was deposited onto a quartz reflector surface, previously rendered hydrophobic with silicone–IPA solution, and dried under vacuum at 25 °C for 1 min. Detection and IS calibration used the Hg Lβ line (11.82 keV) as the Hg Lα line (9.99 keV) partially overlaps the Ga Kβ line (10.26 keV). The LOQ was 70 ng L−1 with an RSD of 0.12% at 100 ng L−1; and the enhancement factor was 68. In these days where occupational health and safety is paramount, the use C6H6 to achieve such good sensitivity may well be questioned by some.
Several uses of TiO 2 nanofibres were demonstrated for use with dispersive micro-SPE (DMSPE) in speciation studies. In one application, Chen et al.32 synthesised the nanofibres by initially mixing MeOH (98%, 9 mL), acetic acid (99.5%, 0.3 mL) and Ti(BuO)4 (98%, 2.0 g), poly(vinyl pyrrolidone) (0.56 g) before further vigorous mixing for 4 h to form the TiO2 sol. This was loaded into a syringe needle connected to 12 kV dc and the fibres produced by electrospinning were annealed at 500 °C for 3 h. Sonication was used to promote adsorption of SbV onto the nanofibres (0.6 mg; 5 mL sample at pH 5.0) which was then desorbed with HNO3 (0.5 mol L−1, 2 mL) and diluted to 5 mL while SbIII stayed in sample solution. These Sb species were subjected to DLLME by adding a chelating reagent (ADPC, 100 μL) with mechanical and ultrasound mixing followed by dispersant (EtOH, 200 μL) and extraction solvent (CHCl3, 15 μL). After phase separation by centrifugation (5000 rpm, 3 min) an aliquot of sedimented phase (10 μL) was analysed by ETV-ICP-MS. The EF was 400 and LOQs for SbIII and SbV were 0.063 pg mL−1 (1.9 pg g−1) and 0.083 pg mL−1 (2.5 pg g−1), with RSDs (at 1.0 ng mL−1, n = 9) of 5.7% and 6.9%, respectively. The trueness was assessed against tea leaves CRM (GBW07605) with recoveries in the range of 94–104%. The potential interference of the following ions from biological matrices was deemed to have no significant effect on the extraction and determination of the analytes: Cl− and NO3− (2000 mg L−1); SO42−, SiO32− and PO43− (1500 mg L−1); K+ and Na+ (3000 mg L−1); Ca2+ and Mg2+ (2000 mg L−1); Al3+ and Fe3+ (2 mg L−1). Analysis of green tea leaves indicated that two thirds of the total Sb (0.43 ng mL−1) was inorganic with the majority as SbIII. In a different implementation of TiO2 nanofibres in DMSPE-DLLME by the same authors,33 the nanofibre adsorbant (60 mg) was put into a microcolumn and conditioned with HNO3 (1.0 mol L−1, 5 mL) and H2O (10 mL) then the digested tea sample (20 mL) was loaded onto the column. The chelating reagent used was 1-(2-pyridylazo)-2-naphthol (8 × 10−3 mol L−1); EtOH (0.5 mL) and CCl4 (50 μL) were used as dispersant and extraction solvents in DLLME. An aliquot of sedimented phase (10 μL) was analysed by ETV ICP-MS. The EF was 450 and LOQs for TlI and TlIII were 0.015 pg mL−1 and 0.020 pg mL−1, respectively, with RSDs (at 1.0 ng mL−1, n = 9) of 6.5% and 7.3%, respectively. The potential ionic interferents detailed above were also demonstrated not to influence the results. Analysis of green tea leaves indicated that 44% total Tl was inorganic with the majority as TlI. The use of CCl4 contrasts against the “green” procedures noted above.
Modified Graphene oxide (GO) was also used in magnetic SPE for the extraction of total Pb in a variety of food and drink matrices.34 The production required its initial dispersal in DMF and reflux with thionyl dichloride for 24 h followed by functionalising with 4-(2-pyridylazo)resorcinol (PAR). After washing and drying the GO–PAR was grafted to magnetic NPs by heating (80 °C) under N2 with FeCl3 and FeCl2 and adding NH4OH to precipitate the GO–PAR@Fe2O3 NPs which could be separated with a strong magnet. The GO–PAR@Fe2O3 nanocomposite (1 mg) was dispersed in H2O (1 mL) with ultrasound then injected into the sample (30 mL), adjusted to pH 5.0, from which it was separated using a magnetic field, washed with MeOH–H2O and the Pb desorbed with HCl (0.4 mol L−1, 50 μL). Determination was by ETAAS. The sorbent capacity was 133 mg g−1 which gave an EF of 600, an LOD of 0.18 ng L−1 and an RSD of 2.4% (at 20 ng L−1, n = 7). Recovery of Pb from the clean water CRM ERA 1340 was 98.8% ± 1.7%, while the influence of other elements was assessed by recovery: for Cr and Cu recovery was 30 and 29% respectively and other elements (As, Cd, Co, Fe, Mn, Ni, Se and Zn) were <17% showing relatively good specificity. The method was applied to water, fruit juice and rice samples collected in Iran with spiking showing recoveries between 94.3% (well water) and 107% (apple juice).
A new magnetic ionically-imprinted nanosorbent for Cu preconcentration with 3-hydroxy-2H-indol-2-one (isatin) as a ligand was synthesised by Dahaghin et al.35 Magnetic NPs were first prepared with Fe2+ and Fe3+, as above, and functionalised with 3-vinyltriethoxysilane in DMSO. The nanosorbent was constructed around a Cu2+ template with isatin and 4-vinyl pyridine ligands onto which the vinyl-functionalised magnetic NPs were cross-linked with ethylene glycol dimethacrylate. After reflux under N2 at 70 °C for 24 h, the nanosorbent was isolated with a magnetic field and washed with MeOH. The template Cu2+ was then eliminated with HCl (2 mol L−1). The conditions for preconcentration were a sample volume 200 mL adjusted to pH 6, 15 mg nanosorbent, elution with HCl (2 mol L−1, 3 mL) over 10 min. The sorbent capacity was 83 ng g−1 with an EF of 200. When coupled with FAAS, the LOD was 0.13 μg L−1 with an RSD of 3.4% at 30 ng mL−1 and the recovery of Cu spikes (10 ng mL−1) was 97–98%.
4 Progress with analytical techniques
4.1 Mass spectrometry
Increased sensitivity for determination of Pb in food was achieved in a study by Guerin et al.16 by way of a programmable temperature cyclonic spray chamber, which was maintained at 35 to 45 °C rather than 2–3 °C as with a conventional spray chamber. Significantly lower LOQs with respect to other studies using ICP-MS were obtained (0.6 and 0.9 μg kg−1 for liquid and solid foods respectively). The method was validated using three food-based CRMs and then applied to 291 samples in the French Total Diet Study in Infants and Toddlers. Helium as collision gas, is routinely employed in ICP-QMS to aid removal of polyatomic interferences by kinetic energy discrimination, usually at the expense of reduced sensitivity. The report of Panova et al.36 which described an optimised method for 202Hg in urine using He, and achieved more than double S/N ratios with respect to no gas mode, attracts attention. This unexpected observation was speculated to be because of better focusing of the ion beam and a negligible effect of kinetic energy discrimination on high mass Hg. However, the work needs to be read with caution as there are several basic errors. For example, the He gas flow was optimised at 4.925 mL min−1 to minimise polyatomic interference from W compounds (e.g., 186W16OH), but this species as written has a mass of 203 and should be given as 186W16O! Analytical figures of merit were an instrumental LOD of 2 ng L−1, LOQ in urine of 0.15 μg L−1, spiked recoveries of 90 to 110% and RSD of 4.6% at 25 ng L−1.Two non-standard couplings with ICP-MS were seen in this review period, both for the purpose of facilitating speciation analysis. First, two complimentary papers reported use of ETV-ICP-MS for determining Sb33 and Tl37 species in tea infusions, following separation and pre-concentration of the species by SPE with TiO2 nanofibres and DLLME. The DLLME strategy would not be compatible with conventional liquid nebulisation due to the low tolerance of ICP-MS for organic solvent but ETV facilitates removal of the organic matrix as well as affording high sample introduction efficiency. After optimisation of the pyrolytic graphite tube ETV procedure, good ERs (450 and 400 for Tl and Sb respectively) and LODs (0.015 to 0.020 pg mL−1 for TlI and TlIII; 0.019 and 0.025 pg mL−1 for SbIII and SbV) were achieved. Satisfactory results were obtained for a tea leaf CRM. The second coupling involved selective HG with cryotrapping and ICP-MS for direct speciation of As in blood and plasma at low exposure levels (<1 μg L−1).38 Use of ICP-MS provided more sensitive detection than AAS while HG-cryotrapping separated analytes from the liquid matrix necessitating minimal sample preparation. Addition of Triton X-100 and Antifoam B to sample dilutions overcame an issue with foam formation in the hydride generator, which led to low recoveries and memory effects, while inclusion of reducing agent, L-cysteine, enabled the sum of trivalent and pentavalent As species to be determined. For iAs and methylated As species respectively, LODs in blood/plasma were 0.014 and ≤0.002 μg L−1 and LOQs were 0.047 and ≤0.008 μg L−1, which compared favourably with those reported for HPLC-ICP-MS methods. Excellent RSDs (<5%) were observed as well as good recoveries compared with phosphoric acid digestion and HG-cryotrapping-AAS (91 to 99% in blood; 88 to 104% in plasma).
In a study evaluating the maximum bioavailability of elements (As, Cd, Cr, Cu, Fe, Ni, Pb and Zn) from wheat, an online, continuous leaching front end system was coupled to ICP-MS.39 Artificial digestive fluids (saliva, gastric juice and intestinal juice) at 37 °C were sequentially pumped through a mini-column packed with wheat powder (4 g) before directly entering the ICP-MS nebuliser and continuously monitored for the released elements. Use of a larger column than in previous work led to an improvement in reproducibility and decreased back pressure. The approach produced comparable results to batch analysis but with much shorter analysis times (15 min versus >4 h) due to the more efficient leaching process due to the constant exposure of fresh reagent to the wheat. Polyatomic interferences were mitigated using H2 reaction gas. A wheat flour CRM was utilised to assess accuracy of the method, which was then applied to 6 wheat samples from Saudi Arabia.
This year a particularly interesting piece of work involved use of ICP-MS/MS to attain adequate interference removal in the measurement of the radionuclide 210Pb in drinking water as a rapid alternative to radiometric approaches.40 Although the WHO has very restrictive guidelines on the allowable concentration of 210Pb in drinking water, routine monitoring is not performed owing to the lack of sensitive and high throughput techniques for measurement. The suitability of stable Pb isotopes as calibration standards rather than radioactive sources as a cheaper and more practical approach was demonstrated. Assessment of interferences using mono-elemental solutions with monitoring of m/z 210 at each quadrupole and no reaction/collision gas showed no significant interference from isobaric 210Bi and 210Po, but increasing polyatomic interference associated with Hg < Pb < Er < Bi < Pt. This necessitated chemical separation of these elements particularly as pre-concentration of 210Pb was required to achieve adequate LODs. For the two extraction protocols compared: combined co-precipitation with Fe(OH)3 and extraction chromatography on an Sr resin (CoP-EXC) versus an in-house designed CPE system using a crown ether ligand and back extraction with ammonium citrate (BE-CPE). Both methods achieved similar LODs and LOQs at 5 fg L−1 and 15 to 17 fg L−1 respectively and below statutory limits. The BE-CPE method was favoured, however, owing to higher extraction efficiency for Pb (83 versus 61%) with a superior level of selectivity, increased pre-concentration factor (78 versus 60), higher throughput (36 versus 8 samples) and shorter turnaround times (4.5 h versus 1 day). The use of ICP-MS/MS was also applied to improve the sensitivity of Se measurement in conjunction with ion pairing RP-LC to determine inorganic and organic Se species in rice.41 Following comparison of chromatography approaches, the reaction gases H2 and O2 and collision gas He were evaluated using a 10 μg L−1 Se standard. Highest sensitivity (3 to 5-fold that with O2) and lowest background signal was observed with H2. The recoveries of all five Se species spiked in blank rice, following extraction with protease and lipase, were between 75 and 114% with RSDs ≤9.4%. Method LODs were 0.02 to 0.12 μg L−1 and LOQs, 0.1 to 0.4 μg L−1.
A review article focusing on spICP-MS in the context of bioassays highlighted some of the challenges to ICP-MS instrumentation, in particular with regard to multi isotope analysis of transient signals from individual NPs.13 Widely used ICP-QMS and SF-ICP-MS offer adequate scanning speeds and sensitivity for spICP-MS but are too slow to switch between m/z while MC-ICP-MS allows accurate simultaneous detection of isotopes but has restricted acquisition frequency and can’t acquire full mass spectra in a single measurement session. Time of flight ICP-MS, which is capable of simultaneous multiple isotope measurement and can acquire full spectra with very short dwell times, was highlighted as a promising technique in this regard, however, it has not as yet been widely applied to bioassays. A further limitation of low sample introduction efficiency by common solution nebulisers was addressed in a Japanese language paper42 that described the development of a high efficiency nebuliser, consisting of a modified large bore nebuliser, with an internal capillary of 150 μm diameter and a small volume 15 cm3 on-axis cylinder chamber. To validate the approach, 30, 60 and 100 nm AgNPs and 30 and 70 nm PtNPs were measured as total ion concentrations, particle mass concentration, particle number concentration and compared to values provided by the manufacturer.
Two spICP-MS approaches for the determination of TiO2NPs were reported within this review period, achieving successful interference removal by way of ICP-MS/MS and SF-ICP-MS in chewing gum43 and human liver and spleen tissue44 respectively. In the paper by Candas-Zapico et al.,43 ICP-MS/MS was used to monitor 47Ti or 48Ti with either O2 or NH3 reaction gas which showed superior sensitivity and interference removal compared with conventional ICP-QMS detection of 47Ti in any gas mode. Comparing O2 and NH3 reaction gases, O2 mode was more sensitive, yielding a size LOD of 26 versus 32 nm, however, higher backgrounds were observed in chewing gum samples due to the O2 reaction product, [48Ti16O]+, being isobaric with [48Ca16O]+. Therefore, NH3 mode with monitoring of the Ti product ion at m/z 114, interference free, was chosen as the final method. For the dwell time of 10 ms, dilution experiments confirmed that only single particle events were being detected. Determination of the transport efficiency (5.8%) by the particle number method with an Au standard was deemed to be an important limitation to accuracy as Au and TiO2 NPs may not behave similarly. To correct for adsorption of NPs onto extraction vessels, CeO2 was employed as an IS. The optimised ICP-MS/MS method was applied to chewing gum, extracted in an ultrasonic bath, with good agreement observed for the detected particle size with TEM. In the second report,44 human liver and spleen samples following depolymerisation of the formaldehyde fixed tissue and enzymatic digestion with proteinase K, were analysed by SF-ICP-MS with monitoring of Ti at m/z 46.95 to avoid spectral interferences. A dwell time of 2 ms was used. Interestingly, a significantly higher size LOD of 85 nm was reported with respect to the previous ICP-MS/MS study, which may be due to the more complex sample matrix. This hindered estimation of the percentage of TiO2 NPs below 100 nm present in the tissue samples.
Utilising single cell ICP-MS/MS, Meyer et al.45 studied the cellular bioavailability of AsIII in human epithelial lung adenocarcinoma cells. Sample preparation consisted only of re-suspending the cells in water, which does not cause cell membrane permeabilisation. Following the same principle as spICP-MS, in single cell ICP-MS, each cell is detectable as an individual spike signal, allowing both concentration of ions present in a single cell and the number of cells containing the analyte to be determined. A shorter dwell time of 3 rather than 10 ms led to a 2.5 increase in detected cell events, presumably due to reduced detection of co-existences. Only As spike signals more than 3 times the background signal were counted to effectively differentiate noise and cell event signals. Transport efficiency, calculated by counting cells using measurement of S and P concentrations, and comparing this to the known number of cells in the sample, was low at 0.5%; a value comparable to other studies of 10 to 20 μm mammalian cells but representing a limitation requiring use of more efficient sample introduction systems. Successful removal of spectral interferences by monitoring of the O2 reaction product, [75As16O]+, was verified with control cell suspensions. An LOD of 0.35 fg per cell was achieved. Results demonstrated time dependent bioavailability of AsIII in cells as well as differences between individual cells (range 0.4 to 300 fg per cell). Concentrations were generally comparable to those obtained by ICP-MS bulk analysis following acidic microwave digestion.
In a novel study, Xiong et al.46 evaluated microwave plasma torch linear ion trap MS (MPT-LQT-MS) as a cheaper, more rapid alternative to ICP-MS for sensitive measurement of Bi in drinking water, which is also suitable for field analysis. The ambient ion source, MPT, has low power dissipation (<200 W), requires minimal sample treatment and allows high sample throughput. Another useful feature of the methodology is that negatively as well as positively charged ions are formed for most transition metals, which can improve ease of measurement and sensitivity. In positive and negative modes, major peaks corresponding to Bi complex ions were identified using sequential collision-induced dissociation experiments by way of tandem MS. Quantitative analysis was performed under optimised conditions based on the characteristic fragments of the main peaks in the MPT-LQT-MS/MS experiments (m/z 261 and 349 in positive mode and negative mode respectively). Performance was better for negative than for positive mode; for a linear range of 0.5 to 50 μg L−1, R2 was 0.9993 versus 0.9979; the LOD was 0.028 versus 0.193 μg L−1 and RSDs were ≤7.0 versus ≤11.0%. Tap water was analysed along with 5 brands of commercial drinking water using the optimised negative mode method, which had a turnaround time of <5 min. Spiked addition experiments gave recoveries of 83.8 to 113.7%.
4.2 Atomic absorption and atomic emission spectrometry
Few interesting developments associated with AAS and AES, relevant to this ASU, were noted during the last year. Gonalves et al.47 used laboratory-constructed equipment to measure concentrations of Cr and Mn in cow placenta. A tungsten-coil atomiser was prepared from the filament of a microscope bulb and, together with a Czerny–Turner spectrograph and CCD detector, a system to analyse acid digested samples by AES was developed. The LOQs for Cr and Mn were calculated as 8 and 60 μg L−1, respectively with RSDs of 6.5–7.2%. Mean concentrations found in placentae were 0.95 ± 0.22 μg g−1 for Cr and 2.64 ± 0.39 μg g−1 for Mn. Similar values were obtained when samples were also measured by ICP-MS/MS. As discussed in Section 7, two IC methods to determine concentrations of the anticancer drugs, cisplatin and carboplatin, with ICP-AES for detection, were investigated.484.3 Laser induced breakdown spectroscopy
Continuing the trend from last year’s Update,1 a number of publications have demonstrated the benefits of LIBS as a tool for the rapid analysis of food and beverage products. In particular, there was a significant interest in the analysis of infant formula milk. Cama-Moncunill et al.49 described the determination of Na with emphasis on optimisation of the acquisition parameters and calibration strategies using PLS regression. Samples in the range of 0.5–4 mg g−1 Na were used to build the calibration models, with the concentrations previously determined by AAS. The authors concluded that the third-layer spectra normalised by the H I 656.29 nm emission line was optimal, giving a correlation coefficient of 0.93 which was fit for purpose. The same group also published a paper50 following a similar approach but focused on Cu and Fe in infant formula premixes. Due to matrix-based interferences, they again concluded that PLS was the most suitable calibration method using samples which had been characterised for Cu and Fe by ETAAS and FAAS respectively. The range was 0–120 mg kg−1 for Cu and 0–1640 mg kg−1 for Fe and achieved R2 of 0.99. This work went further by investigating the effect of surface contamination by repeatedly analysing the same spot, potentially leading to more accurate results. Chen et al.51 explored the use of modelling statistics for LIBS calibration, using K as the element of interest. The researchers applied a modified ‘random frog’ algorithm in a higher-density discrete wavelet transform domain to pick out the unique features of the K spectra which significantly improved the performance of the PLS calibration model. A correlation coefficient of 0.962 in the range of 0.3 to 0.9 g K per 100 g of infant formula was achieved which balanced favourably with the simple and minimal sample preparation. Following the same analytical approach as the previous papers, Lu et al.52 (in Chinese) described the determination of Cu in tobacco leaf by LIBS and curve fitting models after employing AAS to establish the Cu content as matrix-matched standards. The growing number of publications in this field could be a sign of more widespread acceptance of LIBS as a potential routine technique for quality control and monitoring purposes.In a more unusual application, Bocková et al.53 described a simple approach for the method of liquid samples (wine) by LIBS. The workers added 2 mL of wine to an aluminium polished target and applied gentle heating to evaporate the majority of the liquid, leaving a gel-like thin layer on the surface. The use of aluminium target assisted the induction of the plasma and consequently the breakdown of the gel film. A number of elements were identified by reference to the NIST database of characteristic lines, confirmed by multiple wavelengths, namely Ca, K, Mg and Na as major components and B, Ba, Cu, Fe, Li, Mn, P, Pb, Rb, Si, Sr, Ti and Zn as minor elements. Standard addition calibration was then applied for Fe and Ti although internal standard correction using Ca was also required to account for fluctuations related to the ablation characteristics and variations in the gel film thickness. This significantly improved the R2, typically achieving at least 0.97, with the LOD in the range of 0.1–1.5 mg L−1 and LOQ of 1.5 and 3.5 mg L−1 for Ti and Fe respectively. The authors concluded that the method could be easily expanded to other beverage types due to the simple sample preparation procedure. It is worth highlighting the work of Bonta et al.54 who combined LIBS and LA in tandem with ICP-MS for clinical imaging applications – the reader is referred to the discussion in Section 6.2 for further details.
4.4 Vapour generation procedures and atomic fluorescence spectrometry
Some interesting new developments involving vapour generation techniques were recently reported. Matousek et al.38 described a procedure for speciation of As in blood which involved HG, low temperature capture of the vapour and selective release of analyte for detection by AAS or ICP-MS. The reported LODs were 0.014 μg L−1 for iAs and below 0.002 μg L−1 for methylated As species. The HG-cryocapture-ICP-MS method is appropriate for analysis of plasma and whole blood from individuals with low level exposure. This procedure, and that for the measurement of MeHg and iHg in plant materials,55 are also referred to in Section 6.1. The latter approach involves extraction by closed-vessel microwave heating, formation of ethylated derivatives and measurement by GC coupled to AFS detection via pyrolysis.Atomic fluorescence spectrometry features in all the other reports of interest and all include particularly original features. A novel solid sampling system coupled with AFS was developed by Wang et al.56 for sequential determination of Cd and Hg in food samples. The equipment included a unit at 500–600 °C to vaporise Hg and drive out water and organic substances from the solid sample within a sample boat. An air flow transfers the vapours to a catalytic unit (a combustion tube filled with catalysts made of CaO, KMnO4, Mn3O4 and V2O5), that decomposes the organic gas and smoke from the sample oxidation and absorb halogen and sulfur oxides, at 600–700 °C, while the Hg vapour passes on to a gold-coil trap. The ashed sample in the sample boat is moved to a separate Cd-vaporiser at 1200 °C where an Ar–H2 gas flow takes the Cd vapour to a tungsten coil-trap. With subsequent heating of the traps, the Cd and Hg vapours are released and enter the spectrometer. Timings and temperatures for the various steps were varied to determine the optimum settings and the entire process validated by analysis of CRMs and comparison of results obtained by microwave digestion and ICP-MS. Using 10 mg of sample, the LODs were 0.05 mg kg−1 and 0.07 mg kg−1 for Cd and Hg, respectively with RSDs of less than 15%.
Due to the concern relating to concentrations of Cd in rice, Liu et al.57 developed a simple, cost-effective, and highly sensitive method to determine trace concentrations of this toxic metal in rice. The procedure used a high-efficient liquid spray dielectric barrier discharge-induced plasma (LSDBD) for VG-AFS. Parameters such as discharge voltage and discharge gap and possible interferences by addition of organic substances and foreign ions were investigated. Analysis of the Rice CRM (GBW080684) gave results consistent with the certified concentration. Concentrations of Cd in 11 locally collected rice samples were 7.2–517.7 μg kg−1. Compared with acid-BH4 VG, the proposed method eliminated the use of unstable and expensive reagents and has a high tolerance for coexisting ions.
Zou et al.58 developed an original device to measure low concentrations of Se in mineral water samples. A small photochemical VG unit was constructed from a UV light-emitting-diode (LED) and a quartz coil with nano-TiO2 coating on its inner wall. Conditions for power, temperature, LED wavelength settings and reagent concentrations were investigated. No interferences were found from a range of co-existing ions. The LODs for SeIV and SeVI were 0.28 and 0.21 μg L−1, respectively. Accurate results were achieved for the CRM GBW(E)080395. The key feature of the work described by Ni et al.59 was the sample preparation. In a procedure to measure concentration of As and Pb in vegetable oil by HG-AFS, samples were simply mixed with dilute HNO3 and extracted into the aqueous phase by vortex mixing. The optimised method was investigated for effects of interferents and results compared well with those found when samples were analysed by ICP-MS following microwave digestion. The LODs achieved using this simple and convenient approach were 0.6 and 0.4 μg kg−1.
4.5 X-ray spectrometry
A comprehensive review of recent advances in X-ray spectrometry2,7 complements the applications with clinical and biological materials, foods and beverages covered in this Update. Imaging applications of X-ray spectrometry are described separately in Section 6.2 below.The past year has seen a significant number of noteworthy X-ray spectrometry papers in the clinical field in comparison to the previous Update.1 The use of XRF for the investigation of Gd-based contrast agents are highlighted here, with Section 6.4.4 of this Update providing further insight. Keldani et al.60 described the development of a normalisation procedure for the in vivo determination of Gd in bone by XRF spectrometry, representing a non-invasive analysis technique. Through the use of bone phantoms, they were able to assess the effects of differing tissue depths (0–12.2 mm) to symbolise patient to patient variation. The Gd K X-rays were corrected using the coherent scattered γ-ray from the excitation source. In combination with Monte Carlo simulations, it was concluded that the approach successfully accounted for the influence of tissue thickness and therefore improved the accuracy of in vivo bone Gd measurements. The group continued the research in another publication61 by applying the method in a study comparing individuals with exposure to Gd-based contrast agents within the last 5 years against a control group (both n = 11). Not unsurprisingly, a significant difference (P = 0.01) between the groups was observed with the exposed individuals exhibiting a higher Gd level which was moderately positively correlated with the administered dose (R2 = 0.41). It was also found that Gd was detectable in bone 5 years after the exposure. Following on from Gd, the in vivo determination of Pb in bone using L-shell SR-XRF was presented by Gherase and co-workers.62 The authors noted this approach was first demonstrated 40 years ago yet implementation of the method on a routine basis is hampered by the challenges of sensitivity and calibration. The work compared two different excitation-detection geometries (90° and 135°) using three different X-ray photon energies (15.8, 16.6, and 17.5 keV) and testing with plaster of Paris bone phantoms and resin to represent tissue. The optimal energy and geometries were reported but the use of SR in itself does significantly restrict any potential routine diagnostic application of the technique.
Mankovskii et al.63 described a new application of TXRF for the analysis of Au NPs in cancer cells, as an alternative to ICP-MS. The study utilised the reference material NIST RM 8011 (10 nm Au NPs) and an in-house prepared 10 nm Au NP material, to validate the method and compare the effect of different sample preparation procedures, internal standards and fitting approaches from three software programmes. With the optimal parameters, 4![[thin space (1/6-em)]](https://www.rsc.org/images/entities/char_2009.gif)
:1 v/v HCl:HNO3 and La internal standard and PyMCA fitting software (European Synchrotron Radiation Facility, France), Au NPs were quantified with recovery rates of 102.7 ± 3.7% from solution and 100.9 ± 5.1% from AuNPs incubated with cancer cells. The work demonstrated the novel use of TXRF for the quantitative analysis of AuNPs with small sample sizes (5 μL) and potential applications in clinical diagnostics for cancer markers and therapies. Almeida et al.64 utilised SR-TXRF to study the relationship between soluble β-amyloid oligomers and levels of several elements of interest in Alzheimer’s research. Three groups of mice were exposed to either 10 pmol or 100 pmol soluble β-amyloid oligomers or a control. Six structures of the brain (cerebellum, frontal cortex, hippocampus, hypothalamus, substantia nigra, and temporal cortex) were dissected and digested using HNO3 and H2O2 for the determination of Ca, Cl, Cu, Fe, K, Ni, P, S and Zn. The method was validated using NIST SRM 1577b (bovine liver) which achieved good recoveries given the level of precision. The data showed significant differences in the concentrations of Cu, P and S in the hypothalamus at the 10 pmol level for both male and females groups suggesting an association between Alzheimer’s disease and changes in the concentration of these elements. However, contrary to the authors’ expectations, no statistical differences were observed for Cu, Fe and Zn values in the cerebellum, given that these elements are known to show increased levels in Alzheimer’s patients.
A number of publications in this review period relate to the use of XRF for food and drink analysis. Monticelli et al.65 described the application of TXRF for the analysis of soy sauce after a simple dilution or after acid digestion with HNO3 and H2O2. The presence of organic compounds and the high saline content represented a challenging matrix however the authors reported quantitative data for Cu, Fe, Mn, Rb, Sr and Zn whilst achieving LODs typically <0.5 mg kg−1. It was found that simple dilution had a small bias (−5%) compared with acid digestion but that might be considered acceptable for faster throughput. Oskolok and co-workers31 published a highly sensitive method using TXRF for the measurement of HgII in drinking water in combining with a pre-concentration procedure. Suspended droplet microextraction was employed which produced an LOD of 21 ng L−1 and RSD of 0.12% at 100 ng L−1. Furthermore, interferences from Co, Cr, Fe, Mn, Ni, Pb and Zn were tested up to concentrations of 0.1 g L−1 without effect, although these levels would not be typically expected in drinking water samples.
5 Nanomaterials
As mentioned in Section 1, the number of applications of nanomaterials are rapidly increasing with respect to the topics that are relevant to this Update. This section briefly considers publications that feature nanomaterials in the context of exposure and absorption, as reagents in analytical methods and analysis or characterisation of materials.Campagnolo et al.66 investigated whether inhaled AgNPs reach and cross the mouse placental barrier and induce adverse effects. Exposure for 15 days to 18–20 nm AgNPs for 4 h, at a particle number concentration of 3.80 × 107 particles per cm3 and a mass concentration of 640 μg m−3 cause an increased number of resorbed foetuses compared to mice similarly exposed for 1 h. The animals also had reduced plasma oestrogen and increased placental inflammatory cytokine concentrations. Identification and concentrations of AgNPs in tissues were determined by EDX-TEM and spICP-MS. The implications of these results for human pregnancies was not discussed but would suggest further studies should be undertaken.
Venofer is a product containing FeNPs, for infusion to subjects with iron-deficient anaemia. Using high resolution TEM, dynamic light scattering and UV-Vis spectroscopy, Garcia-Fernandez et al.67 showed the preparation contained NPs with diameter of 15 nm with an Fe core of 4 nm. When incubated with serum or blood the Fe achieved solubilisation levels of up to 42% within 1 h and UPLC-ICP-MS showed binding primarily to transferrin, with virtual saturation of the binding-sites. Residual Fe was found associated with albumin and as smaller-sized particles.
Studies of migration of metal from food contact materials have featured in previous ASUs. Jokar et al.68 examined the behaviour of PEG-coated AgNPs and Ag2+ in food simulants, using single particle ICP-MS. While there was no dissolution of the NPs in 50% EtOH or in low-fat cow milk, it did occur with CH3COOH and a saline solution. Experiments with Ag2+, food simulants and reducing agents failed to show that AgNPs can form from the ion in these settings.
Various NPs are added to foods to improve their quality, sensory appeal, safety and shelf-life, and, hence ingestion is inevitable. In a comprehensive project, DeLoid and co-workers69 proposed a series of studies to investigate interactions of NPs with foods, possible transformations in the gut, absorption and cellular toxicity. A corn oil emulsion was prepared with Fe2O3 NPs and passed through a 3 stage gastrointestinal tract simulator (mouth, stomach and small intestine). Absorption and cellular effects were investigated with an in vitro cell culture model. Measurement of Fe by ICP-MS showed the dissolution of Fe2O3 NPs in the gut and the degree of cellular uptake. The morphology of digestate and small intestinal epithelium cells were examined using TEM and confocal imaging. The results demonstrated that the interactions of the NPs with food and gut components influenced NP fate, transport, biokinetics and toxicological profile. However, toxicity was not seen at the concentrations tested. Cellular absorption of Fe2O3 after 4 h was <1% and approximately 2% for digesta with and without serum, respectively, suggesting that serum proteins alters the biokinetics of NPs. The authors recommended that standardised food models need to be developed to assess the effect of the food matrix on the fate and bioactivity of NPs since commercial foods vary considerably in their compositions and structures.
With the extensive use of NPs in a wide range of clinical and food-based applications, methods for analysis to assess concentrations and distribution are continually being developed and improved. Mankovskii and Pejovic-Milic63 suggested that TXRF spectrometry may be preferred to ICP-MS to measure concentrations of AuNPs in cancer cells as this technique used smaller sample volumes with simpler preparation. The procedure employed digestion in aqua regia, with Y as the internal standard. It was validated using NP RMs and applied to measurements of AuNPs in cultured cells, to mimic the sample type that may be used to investigate delivery of cytotoxic drugs to cancer cells.
Measurement of NPs in foods and tissues was reported by several workers and the use of single particle ICP-MS featured in a number of these. Titanium NPs as food-grade TiO2, is a widely used food additive and there is a need for analytical methods able to detect and quantify such particles. Candas-Zapico et al.43 investigated the potential of ICP-MS/MS for spICP-MS. Using CeO2 MPs as internal standard, performance was compared with single quadrupole mode and superior sensitivity was found, due to more efficient removal of spectral interferences. Particle size LODs down to 26 nm were obtained with ICP-MS/MS. The procedure was applied to investigate TiNPs in extracts of chewing gum, finding particles in the size range of 30–200 nm, with 40% of those smaller than 100 nm. Loeschner et al.70 measured and characterised AlNPs in Chinese noodles. Total concentrations measured by ICP-MS were 5.4 ± 1.9 μg g−1 after enzymatic digestion, and 10.1 ± 2.2 μg g−1 when also digested with HF. Using spICP-MS, the minimum detectable particle diameter was between 54 and 83 nm and 5–18% of the total Al content identified as AlNPs. For a clinical project, Heringa et al.44 measured concentrations of total Ti and TiO2 NPs in 15 post-mortem human livers and spleens. Single-particle HR-ICP-MS was used, alongside SEM with EDXRF spectrometry to demonstrate the presence of NPs in tissue. Half of the concentrations measured were above a level which is considered safe for humans, and more than 24% of the particles seen were less than 100 nm. The authors came to the worrying conclusion that health risks due to oral exposure to TiO2 cannot be excluded.
The positive features afforded by magnetic NPs used as sorbents in methodologies based on dispersive solid-phase microextraction were discussed in the review by Hernandez-Hernandez et al.12 A further application of this approach appears in the work of Yin et al. to determine Pd in pharmaceutical ingredients.25 Glutaraldehyde cross-linked magnetic chitosan nanoparticles were synthesised and characterised by FTIR, XRD and TEM. Parameters such as amount of adsorbent, pH, adsorption time, desorption solutions, and coexisting ions were optimised and performance characteristics determined. The Pd was detected using FAAS and the assay had an LOD of 2.8 μg L−1. A linear range of 5.0–500 μg L−1 was established and recovery of spiked samples was 91.7–97.6%.
Chen et al.37 used TiO2nanofibres in their assay to measure concentration of Tl in tea leaves and tea infusions by ETV-ICP-MS. The SPE step with the nanofibres separated Tl from polyphenols, soluble sugars, catechin, caffeine and tea pigments and, after elution with dilute HNO3, further enrichment was achieved by DLLME. The LOD was 0.015 pg mL−1 with an RSD of 6.5% at a concentration of 0.10 ng mL−1. Results for a tea leaves CRM agreed with the certified value.
6 Applications: clinical and biological materials
6.1 Metallomics
A comprehensive review of recent advances in speciation and related applications4 accompanies this update and includes applications with clinical and biological materials, foods and beverages. The review by Wang et al.10 discussed ICP-MS-based methods for determining trace elements and their species in cells suggesting that these will increasingly benefit biomedical research and clinical applications.Noting that absorbed Cd2+and Hg2+enter the circulation and are taken into red blood cells, where binding occurs to glutathione (GSH) and haemoglobin, Gibson et al.71 theorised that these interactions may be relevant to haemolysis. To characterise such interactions, SEC-ICP-OES was used to separate components of mixtures of red cell lysate with Cd and Hg species. In these experiments, a reducing environment was maintained by adding 2.5 mM GSH to 100 mM Tris buffer mobile phase at pH 7.4. It was found that Cd bound predominantly to haemoglobin with small amounts eluting with GSH whereas almost all the Hg was associated with GSH. The authors considered the fate of Hg intrinsically linked to the metabolism of Fe species.
Two novel approaches to determine species of As, both with AAS or ICP-MS for quantification, were noted during the last year. Together with colleagues from the Czech Republic, China and the USA, Matousek38 developed a sensitive procedure to measure concentrations of As species as low as 0.002 μg L−1, in whole blood and in plasma. Selective HG with cryotrapping, coupled to either an AA spectrometer with quartz atomiser or to an ICP-mass spectrometer were used to analyse samples simply diluted 1 + 4 with Triton X-100, Antifoam B and L-cysteine. Results obtained using this straightforward procedure for sample preparation were equivalent to those determined after mild phosphoric acid digestion. Recoveries from spiked samples, at concentrations of 0.15–0.4 μg L−1, were 88–104%. Torres et al.72 focussed on As species in extra virgin olive oils. Samples with increased total As concentrations, determined by ICP-MS after microwave digestion, were taken for SEC-ICP-MS and the fraction at 66 kDa collected for further analysis. The free and protein-bound As were then separated using molecular weight cut-off filters and the As determined by ETAAS. The protein-bound fraction was further separated by AEC with ICP-MS to determine the DMA and As3+.
Methods for the speciation of Hg in various sample types continue to be reported. An unusual approach to Hg speciation in fish was described by Senila et al.73 Rather than employing chromatographic separation, a procedure with double liquid–liquid extraction (47% HBr, toluene, 1% L-cysteine) was used with thermal desorption AAS to determine MeHg. Total Hg concentrations were given when the sample was not extracted. The method was validated by analysis of CRMs. The LODs were 0.02 and 3.0 μg kg−1 for total and MeHg, respectively. It is now recognised that MeHg can be absorbed by plants with the implication that foods such as rice may be a source for human exposure. Jimenez-Moreno and co-workers55 therefore developed a fast, sensitive method for simultaneous determination of iHg and MeHg in rice and other aquatic plants. Hg species were extracted, ethylated and separated by GC with pyrolysis-AFS for detection. Recoveries from spiked plants and CRMs were 92–101% and the LODs were 0.7–1.0 ng g−1. The entire procedure was simple and rapid, with the analysis of CRMs giving results consistent with the certified values.
Although identification of new Se species seems to have declined in recent years a group of researchers in Spain appeared to be attempting the world record for the number of species measurable in selenised yeast.74 Low Mr species in ultrasound assisted water extracts were identified by ICP-MS as they eluted from a SEC column, and then subjected to LC-TOF-MS, using positive ion mode ESI. With this technique, 103 species of size 300–650 Da were detected. Gao et al.41 were somewhat more restrained with their procedure to separate organic and inorganic Se species in rice by ion-pairing RP chromatography combined with ICP-MS. Separation was shown to be superior when ion-pairing RP chromatography was used compared to AEC. Particularly sensitive LODs at 0.02–0.12 μg L−1 were achieved for the five Se species that were found.
6.2 Imaging: LA-ICP-MS and XRF spectrometry
Within this year’s review period, a significant number of articles in the clinical area were published covering a wide range of applications, perhaps indicating the maturity of the technology in this field. The use of LA-ICP-MS for the investigation of Wilson’s disease was featured in two works by Hachmöller and co-workers.75,76 In the first,75 the researchers studied the effect of the copper chelator D-penicillamine, used in the management of the condition, with LA-ICP-MS. High resolution images of the Cu distribution in rat liver tissue, collected with a 10 μm spot size, were compared for those treated with the drug and controls. Elevated Cu concentrations were found in those without the chelation therapy and Cu hotspots were observed. The Cu levels were more than 2-fold lower in the treated animals, yet the distribution was highly inhomogeneous in direct proximity to blood vessels. Furthermore, a human liver needle biopsy was analysed from a patient receiving the D-penicillamine therapy which confirmed the inhomogeneous Cu results from the rat models. In the second paper,76 the effect of histological staining techniques on Cu levels and distribution were investigated with LA-ICP-MS. An evaluation of the common stain haematoxylin and eosin, and rhodanine, which is used specifically for the diagnosis of Wilson’s disease, was performed to obtain both qualitative and quantitative data after calibration with doped gelatine standards. Liver needle biopsy samples from patients were analysed as unstained and rhodanine treated, finding that the stained tissues had between 20% to >90% lower Cu concentrations, and that the distribution in the stained samples resulted in a “blurring” of the images. The authors speculated the rhodamine removed Cu during complexation, as one sample treated with the haematoxylin and eosin stain, showed no such decrease in Cu concentration or visibly affected the distribution. Therefore, biopsy samples treated with haematoxylin and eosin were considered more amenable to LA-ICP-MS in order to gain further insight to Cu in liver tissue samples of Wilson’s disease patients.Klose et al.77 described a comprehensive in vivo evaluation of potential anticancer compounds based on N-substituted pyridinecarbothioamides with ruthenium (named as plecstatin-1) and its osmium analogue, using LA-ICP-MS. The researchers developed a sample preparation approach in an argon environment to prevent the oxidation of Os to the volatile species OsO4. The effectiveness was demonstrated with spiking studies, achieving an average recovery of 105% for Os and 101% for Ru, inferring no negative effect on Ru. Mouse models were exposed to a colon cancer cell line and split into three groups: control, Ru-treated and Os-treated. Blood, kidney, liver, lung, muscle and tumour samples were harvested and subjected to LA-ICP-MS analysis alongside traditional haematoxylin and eosin staining. Matrix-matched standards prepared from homogenised pig liver were found to be suitable for bioimaging purposes. The spatial distribution across the tissues was in line with expectations, with the highest levels found in the liver and kidney, whereas blood, lung and tumour samples were found at lower amounts and muscle did not appear to accumulate either Ru or Os. The researchers also demonstrated that both compounds showed tumour inhibiting effects however the Os-based drug had a longer lasting influence after drug administration ceased which warranted further investigation as an anticancer candidate. In a publication by Bauer and co-workers,78 online IDA was used as an SI traceable calibration strategy for bioimaging by LA-ICP-MS and was applied to the analysis of Pt in cisplatin exposed kidney tissue. The approach combined the gas stream from LA with a dry aerosol of enriched 194Pt which had been previously characterised for mass flow using reverse IDA. The quantitative data was compared against external calibration from parallel tissue slices and were in good agreement, however IDA offered a number of advantages such as SI traceability, lower uncertainties and element-specific internal standard correction.
A unique opportunity was reported by Fingerhut et al.79 who analysed human brain samples from patients exposed to Gd-based contrast agents. Quantitative imaging with LA-ICP-MS was achieved via gelatine calibration standards with an impressive LOQ of 7 ng g−1 Gd. The high spatial resolution of the technique enabled identification of Gd deposits within different brain regions which, in places, exceeded 800 ng g−1 even two years after the last exposure. The study provided valuable human data in this field.
Attention is drawn to the review of LA-ICP-MS to determine the content and distribution of trace elements on the surface of clinical materials by LA-ICP-MS8 in which the authors considered the metrological aspects associated with sampling, preparation and analysis. Factors such as traceability of calibrators, assay validation parameters and uncertainty of measurements, which are valuable when assessing the reliability of results are often omitted from published work.
The developments of LIBS are highlighted in Section 4.3 however a paper by Bonta et al.54 demonstrated a novel imaging application using tandem LA-LIBS with ICP-MS. This coupling enabled a large range of elemental data to be gathered simultaneously which would not have been possible by either technique alone. The researchers used mouse tumours after treatment with two anticancer drugs (cisplatin and sunitinib) as the model sample to investigate the setup. The measured elements were C, Ca, Cu, Fe, H, K, Mg, Na, O, P, Pt, S and Zn. For C, Ca, K, Mg and Na, the levels were suitable for both techniques and showed good agreement between them (Pearson’s correlation was given as 0.918 for Na). The data provided complementary evidence to support the action of the drugs on the cancer cells with O and P linked to apoptosis and the presence of Pt. Although the work was only qualitative, it represented a novel instrumental step forward for bioimaging applications.
The use of nanoSIMS as a powerful technique to achieve nanometre resolution for cellular and subcellular imaging was presented by Weng and co-workers.80 Contaminated oysters (Crassostrea hongkongensis) were analysed for Cu and Zn which revealed three types of metal-containing cells in the gill and mantle of oysters. Additionally, co-localisation of Ca, N, P and S in haemocyte cells and intercellular haemolymph was found. It was concluded that the metal deposition represented a thermodynamically stable detoxification process utilising metabolised protein pools.
In an overview article highlighting the bioimaging capabilities of the Centre for Ion Beam Applications, CIBA, in Singapore, Ren et al.81 described the two main functions of the facility. The ‘Nuclear Microscopy’ beamline was used predominately for quantitative trace element mapping using a combination of PIXE, RBS and STIM, with a 1–2 μm spot size. The ‘High Resolution Single Cell Imaging’ beamline was equipped a sub-50 nm spot size enabling single cell imaging. Also, forward scattering transmission ion microscopy was utilised to generate images with improved contrast of NPs with higher atomic numbers, such as AuNPs, and proton induced fluorescence was employed to detect fluorescent NPs. A number of biomedical applications for both beam types were also provided.
6.3 Multielement applications
The results reported Hahn et al.83 emphasised the distinction between the effects of metal-on-metal and metal-on-polyethylene implants. Light microscopy and μ-XRF spectrometry studies of 13 undecalcified femoral heads which had undergone surface replacement showed increases in cobalt concentrations, up to 380 μg g−1, compared to control specimens without an implant or with metal-on-polyethylene implants.
Metallosis following total hip arthroplasty is not restricted to human subjects as shown by DiVincenzo et al.84 who reported severe acetabular component wear, implant–bone interface deterioration, and peri-acetabular osteolysis in a dog 4 years after a Ti alloy and Co–Cr total hip arthroplasty. Removed tissue examined by XRF microscopy showed Ti, with smaller amounts of Co, Cr and V.
Ayers and colleagues85 discussed metallosis in patients who had received spinal implants and described their experience with three patients who underwent revision surgery. Signs of fretting corrosion, galling and corrosion fatigue were found on the retrieved implants. Concentrations of Al, Co, Cr, Mo and V in removed tissue, determined by ICP-MS and ICP-OES, were all increased compared to published reference values for muscle.
Gallstones are not uncommon, and it appears that their incidence is increasing, but analysis of biliary fluid is rarely undertaken. Samples of serum, bile and gallstones were collected from 172 patients with the stones classified as cholesterol, mixed and pigmented. Concentrations of Ca, Cu and Fe were determined by FAAS.87 Patients with pigmented stones had significantly higher serum and bile concentrations of Ca, Cu and Fe than the control subjects. It appeared possible that the concentrations of these elements are relevant to the formation of different stone types.
Donati and his colleagues88 used ICP-MS/MS to measure concentrations of 75 elements in urine from 61 patients with urinary tract infection and 26 healthy subjects. The objective was to identify biomarkers for screening, early diagnosis and treatment of this very common infection. From the initial results, Bi, Cs, Mo, Rb, Sb, Sn, Sr, V and Zn appeared to be the most useful biomarkers and, following further analysis, creatinine-adjusted Sb levels were shown to be significantly increased while Mo and V concentrations were significantly lower in the patient compared to control, samples. The authors suggest that these findings offer the potential of using Mo, Sb and V as urine biomarkers for urinary tract infection. However, it is doubtful if this approach will rival conventional microbiological culturing or emerging PCR and molecular techniques.
In two similar papers, a group in Spain described a sensitive procedure to measure concentrations of up to 18 elements in blood, presented as dried spots on filter paper.89,90 Unlike previous reports using this sample type, these workers used LA-ICP-MS for quantification. A focused Nd:YAG laser beam in linear scan mode was used and the analytical conditions were optimised using Seronorm RMs. Various of oxidising agents were investigated and CH3COOH provided the best results. Calibration used matrix-matched samples with 13C and 32S internal standards. The LOQs were from 1.9 μg L−1 to 1094 mg L−1 (the high LOQs refer to Na and other major elements) and results were reported for the Seronorm Level II. The authors included a discussion of the well-known limitations associated with dried blood spots as sample types arguing that these are largely overcome with this procedure. However, the results given for several of the elements in Seronorm Level II indicate that accuracy is not as good as found with other techniques.
Interest in the analysis of bronchoalveolar lavage fluid in the context of occupational exposure to metals and possible disorders of lung function has been noted in recent Updates. As rats are used as a model for experimental studies, Qamar et al.91 determined concentrations of Br, Ca, Cr, Cu, Fe, I, Mg, Mn, Ni, Se and Zn in rat bronchoalveolar lavage fluid by ICP-MS. Various inter-element correlations were identified.
A study that may be seen as complementary to that of Qamar et al.91 was reported by Morton and her colleagues.92 Based within a department primarily concerned with occupational exposure biomonitoring, the objective of the work was to establish normal concentrations of 48 elements in human lung samples, so as to assess pulmonary exposures in case studies. Fresh material was obtained from unaffected areas of lung taken from 54 patients with lung cancer. Concentrations were established by ICP-MS after microwave digestion. The 95th percentiles were calculated for all elements except for Re and were in accord with values available from previous studies. Data were examined for gender, smoking and occupational exposures to metals. Although the focus was on occupational exposure, the work provides a useful database for other studies involving elemental levels in lung tissue.
In a similar study, de Angelis et al.93 also used ICP-MS to measure the concentrations of 44 elements, including REE, in placentae from women with multiple-pregnancies and adolescents with single-pregnancies. Most elements were at greater concentrations in placentae from women with a multiple-pregnancy. Differences in placental content disappeared after adjusting for maternal age. Essential elements did not differ significantly between cohorts whereas concentrations of environmental contaminants were significantly different between groups, even after adjusting for maternal age (Table 1)
| Element | Matrix | Technique | Sample treatment/comments | Reference |
|---|---|---|---|---|
| Ag | Mouse organs, placental and foetal tissue | TEM-EDXRF, spICP-MS | Findings indicated that 18 to 20 nm diameter AgNPs inhaled during pregnancy cross the mouse placental barrier and may be associated with increased expression of pregnancy-relevant inflammatory cytokines | 66 |
| Ag | Human placental tissue | spICP-MS | Enzyme tissue treatment was shown to be superior to alkaline digestion for assessment of PEG or sodium carboxylate surface modified AgNPs in spiked placental tissue. Matrix effects on determination of Ag sensitivity and transport efficiency in spICP-MS were also evaluated | 124 |
| Ag | Guinea pig and minipig wound tissue, liver and spleen | ICP-MS | Assessment of tissue Ag concentrations following treatment with two Ag-based dressings. Negligible Ag concentrations were measured in liver and spleen while wound biopsy concentrations ranged from 0.07 to 19.5 μg g−1 | 125 |
| Ag | Rat blood and tissues | ICP-MS | The Ag and Au distribution in rat blood and organs following administration of Au core/Ag shell nanorods was determined by ICP-MS. Rapid clearance of Ag from blood was observed. At 24 h post intravenous injection, the highest Ag concentrations were found in the liver | 126 |
| As | Cells | Single cell-ICP-QQQMS | Cellular bioavailability of arsenite, following incubation of cells in 25 and 50 μmol L−1 arsenite solutions for up to 48 h, was assessed by single cell-ICP-QQQMS. The LOD was 0.35 fg per cell and the approach was validated by conventional bulk ICP-QQQMS after cell digestion and parallel measurement of S and P | 45 |
| As | Urine | HPLC-ICP-MS | A rise in an As exposure index (18.1 to 37.1 μg L−1), equal to the sum of iAs and metabolite As species, was observed in 1 of 5 workers after handling As-preserved museum exhibits | 127 |
| As | Blood and plasma | HG-CT-ICP-MS | A rapid method, involving minimal sample preparation, was developed for speciation of iAs, MMA and DMA in blood/plasma by way of HG-cryotrapping-ICP-MS. The LODs achieved were 0.014 μg L−1 for iAs and <0.002 μg L−1 for methylated As species | 38 |
| Au | Rat blood and tissues | ICP-MS | See Ag, ref. 126 | 126 |
| Ba | Human teeth | LA-ICP-MS | Evaluation of a calibration approach, incorporating the experimentally derived k coefficient, applicable to the quantitative study of Ba and Sr in historical human teeth | 128 |
| Br | Urine | IC-ICP-MS | Determination of total organic halogen (Br, Cl and I) concentrations in urine by IC-ICP-MS. Sample treatment involved adsorption of the analytes to activated carbon before pyrolysis and the absorption of the gaseous hydrogen halides in aqueous solution. Spike recoveries ranged from 78 to 99%. The method was applied to urine samples from volunteers drinking spring and tap water to assess the influence of disinfection related by-products | 28 |
| Ca | Serum, gall bladder bile, gallstones (cholesterol, mixed and pigmented) | FAAS | Estimation of Ca, Cu and Fe in serum, bile and gallstones from 172 gallstone patients and age matched controls. Element concentrations in serum and bile, as well as bile: serum ratios, were significantly higher in patients with pigmented gallstones compared to those with other gallstone types, and controls. The pigmented gallstones themselves also contained the highest element concentrations | 87 |
| Cd | Red blood cell lysates | SEC-ICP-AES | An investigation into the biochemical fate of Cd2+, Hg2+, CH3Hg+ and thimerosal in red blood cell lysates under reducing conditions | 71 |
| Cd | Blood | AAS | A reference range study for blood Cd, Hg and Pb in the Korean general population including 4000 subjects, aged from 0 to 83 years. Median concentrations of Cd, Hg and Pb were 0.59, 2.87 and 1.83 μg L−1 respectively | 18 |
| Cl | Urine | IC-ICP-MS | See Br, ref. 28 | 28 |
| Co | Myocardial tissue | ICP-MS | Post mortem myocardial tissue from Co/Cr-on-polyethylene total hip arthroplasty patients (n = 75) and controls (n = 73) was analysed for Co and Cr. Significantly higher median Co concentrations were found in hip replacement patients with respect to controls (0.12 vs. 0.06 μg L−1, p < 0.0001) | 82 |
| Co | Femoral heads | μXRF | Analysis of mineralised bone tissue of 13 patients undergoing metal-on-metal hip resurfacing showed higher Co concentrations vs. no implant controls. A maximum Co concentration of 380 ppm was detected 2 years after implantation, indicating rapid accumulation of Co into periprosthetic hard tissue | 83 |
| Co | Horse urine and plasma | ICP-MS | A study to look at using Co:vitamin B12 ratios in urine and plasma as a means to differentiate bona fida supplementation of vitamin B12 and Co doping in horses (n = 6) |
96 |
| Co | Blood and urine | FAAS | A new competitive ligand was synthesised and evaluated for DLLME sample treatment prior to Co detection by FAAS. Following method optimisation, a preconcentration factor of 48, LOD of 4.7 ng mL−1 and LOQ of 15.7 ng mL−1 were achieved. The RSDs were 2.5% and spiked recoveries in blood and urine were 102.5 to 110.0% and 99.8 to 108.9% respectively | 129 |
| Cr | Myocardial tissue | ICP-MS | See Co, ref. 82 | 82 |
| Cr | Cow placenta | Tungsten-coil AES | Concentrations of Cr and Mn in cow placenta measured by W-coil AES showed no statistically significant differences versus microwave-assisted acid digestion and ICP-QQQMS. Method LODs were 2 and 8 μg L−1 for Cr and Mn respectively, RSDs were ≤7.5% and spiked recoveries, 93 to 103%. Mean Cr and Mn concentrations measured in placental tissue were 0.95 ± 0.22 and 2.64 ± 0.39 μg g−1 respectively | 47 |
| Cu | Liver | LA-ICP-MS | A study looking at the influence of two histological stains (rhodanine and, haematoxylin and eosin) on Cu distribution and concentration in 8 liver needle biopsy samples from patients with Wilson’s disease using LA-ICP-MS. Haematoxylin and eosin staining did not appear to decrease or alter the distribution of Cu | 76 |
| Cu | Human and rat livers | LA-ICP-MS | Spatial distribution of Cu, Fe and Zn was investigated in human and rat liver samples after D-penicillamine administration using HR-LA-ICP-MS | 75 |
| Cu | Serum, gall bladder bile, gallstones (cholesterol, mixed and pigmented) | FAAS | See Ca, ref. 87 | 87 |
| Cu | Serum | AAS | Development and validation of a method for direct measurement of free Cu in serum by ultrafiltration with AMIKON® Ultra 100K devices and Cu determination by AAS. The overall procedure had good repeatability and an LOD of 1 μg L−1. When applied to 30 healthy subjects, mean free Cu was 23.6 μg L−1, which corresponded to 2.4% of total Cu | 97 |
| Cu | Plasma | ICP-MS | A method for determination of free Cu in plasma, involving ultracentrifugation and ICP-MS, was developed before being utilized to generate a paediatric reference interval for free Cu (n = 85) | 98 |
| Fe | Human and rat livers | LA-ICP-MS | See Cu, ref. 75 | 75 |
| Fe | Intestinal epithelial cells | ICP-MS | The uptake of Fe3O4 NPs (20, 50, 100 and 200 nm) by intestinal cells under inflammatory conditions was found to be increased compared with control conditions | 130 |
| Fe | In vitro co-culture blood-placenta barrier model | AAS | Time-dependent passage of superparamagnetic Fe3O4 NPs with cationic, anionic or neutral surface charges in a blood-placenta barrier model was studied by AAS alongside magnetic particle spectroscopy | 131 |
| Fe | Serum, gall bladder bile, gallstones (cholesterol, mixed and pigmented) | FAAS | See Ca, ref. 87 | 87 |
| Fe | Blood and serum | ID-ICP-MS, HPLC-ICP-MS | A study investigating the fate of Fe NPs from parenteral formulation, Venofer®, following incubation with blood or serum. Total Fe and Fe species respectively were determined by ID-ICP-MS and, HPLC-ICP-MS in combination with HPLC-UV-vis. Results indicated that up to 42% Fe solubilisation occurred within the first hour and that the main species was Fe bound to transferrin. Quantitative isotope studies estimated that up to 90% of transferrin binding sites were saturated with Fe | 67 |
| Fe | Human, pig, horse and mouse plasma | SEC-ICP-MS | In a study comparing the form of non-transferrin-bound Fe in haemochromatosis patients versus controls, plasma was filtered through a 10 kDa cut-off membrane before being subjected to SEC-ICP-MS. The analysis revealed that the most common Fe species had masses between 400 to 500 Da and no significant differences were noted between the study group and control | 100 |
| Gd | Human brain | LA-ICP-MS | Application of a HR-LA-ICP-MS method to retrospective analysis of brain sections from patients treated with Gd-based contrast agents showed Gd deposits in different brain regions and a highest Gd concentration of >800 ng g−1 more than 2 years after the last dose of contrast agent. An excellent method LOD of 7 ng g−1 was reported | 79 |
| Gd | Bone | XRF | Application of coherent normalisation, which corrects for variation in overlying tissue thickness, to improve in vivo XRF bone Gd measurements in healthy adults | 60 |
| Gd | Bone | XRF | Concentrations of Gd, measured in vivo, in tibia bones of subjects who had previously received Gd-based contrast agents were significantly higher with respect to sex and age-matched controls (1.19 ± 0.73 vs. 1.06 ± 0.71 μg g−1). A positive correlation between dose administered and Gd concentration was also noted | 61 |
| Hg | Red blood cell lysates | SEC-ICP-AES | See Cd, ref. 71 | 71 |
| Hg | Blood | AAS | See Cd, ref. 18 | 18 |
| Hg | Urine | ICP-MS | Use of collision cell gas (He) was found to increase sensitivity of Hg measurement by ICP-MS with respect to no-gas mode. An instrumental LOD of 2 ng L−1 for 202Hg was achieved | 36 |
| Hg | Breast milk | CV-AFS | Total Hg and MeHg were determined in 183 breast milk samples following microwave-assisted acid digestion. For MeHg determination, samples were lyophilised and ethylated before analysis, with an LOQ of 0.1 μg L−1. Mean Hg concentration was 2.56 μg L−1 with MeHg accounting for 11.8% of total Hg | 17 |
| Hg | Vaccines | CV-AFS | A rapid method without need for chromatographic separation was developed for determination of thimerosal and iHg, based on Fe3+-induced degradation of thimerosal with AFS detection. Under optimised conditions, the LODs for thimerosal and iHg were 0.03 and 0.02 μg L−1 respectively. Satisfactory results were obtained for spiked vaccine samples | 132 |
| I | Urine | IC-ICP-MS | See Br, ref. 28 | 28 |
| Mn | Cow placenta | Tungsten-coil AES | See Cr, ref. 47 | 47 |
| Mn | Blood (SRM 3132) | FAAS | A novel preconcentration method consisting of deep eutectic solvent extraction was used prior to Mn determination by FAAS in blood from patients with various neurological disorders. The enhancement factor achieved was 42 and the LOD was 0.29 μg L−1. The method was verified using a CRM | 133 |
| Ni | Urine | ICP-MS | A study comparing urine Ni concentrations in peritoneal dialysis patients (n = 50) and healthy controls followed by correlation with clinical outcomes and inflammatory markers. The dialysis patients had higher urine Ni concentrations than controls (6.1 ± 3.5 vs. 2.8 ± 1.4 μg L−1) and urine Ni concentrations in this group were positively correlated with serum C-reactive protein levels. However, there were no differences in clinical outcome associated with urine Ni concentration | 134 |
| Ni | Urine | ICP-MS | Concentrations of urine Ni were measured in pregnant women in China (n = 7291). After adjusting for potential confounders, each doubling in Ni concentration was associated with a 16% increase in the adjusted odds ratios for preterm delivery | 102 |
| Os | Mouse liver, kidney, muscle and tumour tissue | LA-ICP-MS | The spatial distribution of two anti-cancer drugs (organoruthenium plecstatin-1 and its isosteric Os analogue) was determined by LA-ICP-MS in treated mice. Bulk concentrations of Os and Ru, obtained following microwave digestion and ICP-MS, were in good agreement with LA-ICP-MS results. Highest metal concentrations were found in the liver | 77 |
| Pb | Bone | XRF | Bone levels of Pb assessed by in vivo XRF in Canadian volunteers (aged 1 to 82 years) between 2009 and 2011 were compared to results obtained 17 years previously and showed a reduction in tibia Pb content of 36 to 56% in adults. Bone Pb levels of individuals were observed to fall over the time period and a t1/2 of 7 to 26 years was estimated | 101 |
| Pb | Blood | AAS | See Cd, ref. 18 | 18 |
| Pt | Rat kidney | LA-ICP-MS | A new calibration strategy for elemental bioimaging, based on online IDA and LA-ICP-MS, was applied to determination of Pt in rat kidneys following cisplatin perfusion studies | 78 |
| Ru | Mouse liver, kidney, muscle and tumour tissue | LA-ICP-MS | See Os, ref. 77 | 77 |
| Se | Whale cardiac and liver tissue | LC-ICP-MS | Selenium proteins were separated and detected by multi-dimensional LC-ICP-MS (SEC/UV) and identified with LC-ESI-MS/MS in heart tissue (n = 5) and liver tissue (n = 30) of pygmy sperm whales with and without cardiomyopathy. Metallothioneins were found to be associated with Se and were present in greater abundance in animals with cardiomyopathy versus those with no pathological findings | 135 |
| Se | Bovine semen | ICP-MS | Rapid sample preparation involved solubilisation in 10% v/v formic acid and led to a 50% increase in Se signal. No difference in results was seen compared with microwave-digestion | 24 |
| Se | Serum | AAS | Study of serum Se concentrations in children receiving an olive oil-based ketogenic diet (mean age 7.3 ± 4.2 years, n = 110). Mean Se levels were significantly lower at 6 and 12 months of treatment compared with baseline (66.2 ± 23.3 and 57.2 ± 16.2 versus 79.3 ± 25.7 μg L−1) and 49.1% of patients were diagnosed with Se deficiency (Se < 48 μg L−1) | 103 |
| Se | Serum (SRM 1950) | LC-ICP-MS | A 5 minute method, developed for quantitative determination of selenoprotein P, involved affinity chromatography separation with ICP-MS detection. The method was validated using a CRM before being applied to 50 occupationally non-exposed people living in Northern Germany. The mean selenoprotein P concentration measured was 46.2 (range 31.1 to 59.7 μg L−1), which was equivalent to 58% of total serum Se | 136 |
| Sn | Urine | ICP-MS | A study to evaluate demographic, socioeconomic and lifestyle factors associated with total urine Sn levels in adults (n = 3522) and children (n = 1641) participating in the NHANES 2011 to 2014 health survey. Median urine Sn concentrations were 0.42 μg L−1 in adults and 0.60 μg L−1 in children | 104 |
| Sr | Human teeth | LA-ICP-MS | See Ba, ref. 128 | 128 |
| Ti | Human liver and spleen | SP-ICP-HRMS | Quantification of total Ti and TiO2 NPs in 15 post-mortem liver and spleen samples was performed by spICP-MS. At least 24% of the TiO2 NPs had a diameter <100 nm | 44 |
| Zn | Human and rat livers | LA-ICP-MS | See Cu, ref. 75 | 75 |
| Various (48) | Human lung | ICP-MS | The 95th percentile concentrations of 48 elements were reported in microwave-digested lung tissue from 54 hospital patients | 92 |
| Various (46) | Human placenta | ICP-MS | Elemental concentrations in placentas from adult women carrying multiples were found to be generally higher with respect to those from adolescents carrying singleton pregnancies. A significant association was also noted between element concentrations and maternal age. Nutritionally essential elements did not differ between the two groups whereas environmental contaminants did, even after adjusting for maternal age | 93 |
| Various (8) | Embryonic tissue | MIP-AES | The elemental content (Al, Cd, Cr, Cu, Mn, Ni, Pb and Zn) of miscarried embryonic material (n = 20) was determined by MIP-AES and reviewed in the context of the mothers’ smoking status, dietary patterns and place of residence | 137 |
| Various (6) | Mouse brain | TXRF | Distributions of elements Cu, Fe, K, P, S and Zn were evaluated by TXRF (using an 11.5 keV monochromatic beam) in the brains of mice given a single intracerebroventricular injection of beta-amyloid oligomers to induce experimental Alzheimer’s disease. Differences were seen in elemental concentration between the Alzheimer’s disease and a control group | 64 |
| Various (4) | Dog periarticular tissue | XRF microscopy | Laser capture microdissection followed by XRF microscopy indicated that soft tissue surrounding a total joint hip replacement, consisting of a Ti alloy and CoCr total hip system, contained large amounts of Ti with smaller amounts of V, Co and Cr. These findings, along with characteristic gross and histological lesions, confirmed a diagnosis of metallosis in a dog | 84 |
| Various (11) | Rat bronchoalveolar lavage fluid | ICP-MS | Various elements were measured in the lung lining fluid of rats. Calcium (6318.08 ± 3094.3 μg L−1) and Cu (0.89 ± 0.21 μg L−1) were found in the highest and lowest concentrations respectively. No correlation was found between element concentrations and cell counts but some significant correlations were identified between element concentrations | 91 |
| Various (6) | Aqueous humour | FI-ICP-MS | Trace elements (Cd, Co, Cu, Mn, Fe and Zn) were determined in aqueous humour of patients with primary open-angle glaucoma (n = 12), psuedoexfoliation glaucoma (n = 10) and controls (n = 11). Patients with glaucoma had significantly higher concentrations of Zn versus controls and those with primary open-angle glaucoma had significantly lower levels of Fe | 86 |
| Various (19) | Blood | SF-ICP-MS | Concentrations of 19 elements were measured in blood as part of a biomonitoring survey in Italian adolescents (n = 453). An exposure assessment following an exposome approach was then conducte | 20 |
| Various (10) | Blood | ICP-MS | A reference range study of trace metals (Al, As, Cd, Cs, Cu, Hg, Mn, Pb, Se and Zn) in a Korean population (n = 258, aged 12 to 78 years). Significant gender related differences in metal concentrations were found and levels of Al, As and Hg were noted to be high compared with other population studies | 19 |
| Various (8) | Serum | ICP-MS | Serum concentrations of Co, Cr, Cu, Mn, Mo, Ni, Se and Zn were compared across two reports in 80 professional athletes and 31 sedentary residents of the same geographic area. Higher concentrations of Cr, Mn, Mo and Ni but lower concentrations of Se were found in sportsmen versus controls. Within the sportsman group, the elemental concentrations varied between the aerobic, anaerobic and aerobic-anaerobic exercise groups | 138 and 139 |
| Various (19) | Dried blood spots (Seronorm™ level II) | LA-ICP-MS | An LA-ICP-MS method for multi-elemental analysis of dried blood spots, using a focused Nd:YAG laser beam in linear scan mode, was validated and acceptable precision and accuracy demonstrated. The LOQs ranged from 1.9 μg L−1 to 1094 mg L−1 | 89 |
| Various (16) | Dried serum spots | LA-ICP-MS | Direct multi-element determination of 16 elements in dried serum spots, with sampling at 2.7 mm diameter, achieved LOQs from 21 to 221 μg L−1 and RSDs ≤12% for all analytes. To validate the method, several CRMs were analysed before the method was applied to samples from healthy adults | 90 |
| Various (7) | Dried blood spots | ICP-MS | Determination of As, Cu, Fe, K, Mg, Se and Zn in dried blood spots was found to be precise and accurate for most elements using spiked blood but only a weak correlation with whole blood was observed. Haematocrit was demonstrated to influence the elemental concentrations measured, particularly for K, Fe and Zn | 140 |
| Various (9) | Urine | ICP-MS/MS | Use of ICP-MS/MS to identify potential biomarkers for urinary tract infection using urine from 61 affected patients and 26 health volunteers. Of 75 analytes initially evaluated, nine (Bi, Cs, Mo, Rb, Sb, Sn, Sr, V and Zn) were accurately determined in all samples. The LODs ranged from 0.9 to 100 ng L−1 and spiked recoveries were 90.7 to 104%. Differences in concentrations of Mo, Sb and V between the two groups reached statistical significance | 88 |
| Various (18) | Hair | ICP-MS | Establishment of reference values for hair from healthy children (n = 648) in a Spanish population | 21 |
| Various (12) | Human and cow’s milk (human milk NIST SRM 1953) | ICP-MS/MS | A dilute and shoot approach for determination of 12 elements in low volumes (<250 μL) of human and cow’s milk using ICP-MS/MS. Recoveries for the CRM were 93 to 108% with the exception of Mn, which showed over-recovery at 151% | 141 |
| Various (9) | Breast milk | ICP-MS | A rapid alkaline sample dilution method was compared to acid digestion for measuring elements (Ca, Cd, Fe, I, Li, Mg, Na, Se and Zn) in human breast milk samples (n = 237). Higher analytical precision with similar LODs and recoveries was reported | 23 |
6.4 Progress for individual elements
Hillyer et al.96 attempted to distinguish Co doping from legitimate supplementation by measuring both vitamin B12 and Co in equine samples. Unlike humans, horses are able to synthesise vitamin B12 but require Co in their diet to do so. Supplements that contain both vitamin B12 and Co salts are considered legitimate but may cause false positives in doping tests based on Co concentration cut-offs. The authors conducted a pharmacokinetic study in six thoroughbred horses dosed with a legitimate supplement (containing 1.5 mg vitamin B12 and 7 mg Co gluconate) or 100 mg CoCl2. Urine and plasma samples were collected at various times pre and post dosing; Co was measured by ICP-MS and vitamin B12 by immunoassay. The authors concluded that the measurement of Co:vitamin B12 ratio may be a useful addition to the current testing regime.
One area of Gd research that has featured heavily in previous editions of this review has been the development of XRF spectrometry methods for the non-invasive measurements of Gd in bone, and two papers discussed here add to this literature. Keldani et al.60 investigated whether coherent scatter correction XRF spectrometry can compensate for intra-individual variation in the thickness of tissue over the bone. Experiments with Gd-doped plaster of Paris phantoms and Monte Carlo simulations suggested that the correction method was useful. A subsequent study from the same research group61 tested the method in human study participants: 11 with known Gd contrast agent exposure and 11 matched unexposed controls. Bone Gd concentrations that were significantly higher than controls were detected in 4 out of the 11 exposed individuals. Interestingly, 3 of these participants had only a single dose of Gd-based contrast agent 5 years previously, demonstrates the stability of Gd in bone. A correlation between Gd dose (gadobutrol) and bone Gd was also seen (R2 0.41, P-value 0.003).
7 Applications: drugs and pharmaceuticals, traditional medicines and supplements
In response to the guidelines of the United States and the European pharmacopeia, plus the International Conference on Harmonization (ICH) regulating elemental impurities limits in pharmaceuticals, Chahrour and co-workers105 reported the development of a method that overcomes low recoveries of Os spiked into samples, and allowed the determination of all United States Pharmacopeia-required elemental impurities (As, Cd, Cr, Cu, Hg, Ir, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru and V) in a single analysis. The assay was applied to the analysis of a new antibiotic, TP-6076. As described in Sections 3.2.1 and 5, Yin et al.25 also developed and validated a procedure for measuring concentrations of Pd in active pharmaceutical ingredients.In contrast to the usual HPLC approach, Zachariadis and Misopoulou48 developed two non-suppressed IC methods to determine concentrations of cisplatin and carboplatin in urine. The methods use either anion or cation columns but the latter, with a Shodex IC YK-421 (4.6 × 125 mm2) column, was preferred. Using a tartaric acid–boric acid mobile phase at a flow rate of 1 mL min−1, separation occurred in 2 minutes. The LOD for both drugs was 0.1 mg L−1. An additional Pt peak, assumed to be a hydrolysis product of cisplatin, appeared following the primary peak.
Determination of the organic composition of heroin using conventional procedures fails to differentiate heroin samples from South America or Mexico. DeBord et al.106 showed that the 87Sr:86Sr ratio, determined by MC-ICP-MS following microwave assisted acid digestion and ion exchange, could correctly differentiate the origin in at least 77% of the tested samples. This is believed to be the first time Sr isotope ratios have been used to assess the provenance of heroin samples. The work also reports the 87Sr:86Sr ratio in NIST SRM 1570a (spinach leaves) for the first time.
A method to determine concentrations of Br and I in medicinal plants that meet the requirements of the United States Pharmacopeia (<125 μg g−1) was developed and verified by Nascimento and colleagues.107 Samples, 1000 mg pressed as pellets, were digested by microwave-induced combustion at 20 bar of O2. Residues were taken into 50 mmol L−1 NH4OH and refluxed for 5 minutes, achieving close to 100% recovery. Concentrations in the final solutions were determined by ICP-MS. The large sample weight afforded low LOQs (0.033 μg g−1 and 0.003 μg g−1) for Br and I, respectively. Accuracy of results was demonstrated by analysis of CRMs and by recovery experiments.
8 Applications: foods and beverages
8.1 Progress for individual elements
| Element | Matrix | Technique(s) | Sample preparation/comments | Ref. |
|---|---|---|---|---|
| Ag | Food simulants, cow milk | spICP-MS | The migration of AgNPs into conventional food simulants (10%, 20% or 50% EtOH, 3% acetic acid, olive oil) and low fat cow milk was investigated before and after incubation for 4 h or 10 days at 40 °C | 142 |
| Al | Chinese noodles | spICP-MS | AlNPs were detected in all of 21 samples after enzymatic digestion by amylase | 70 |
| Al | Infant parenteral nutrition solutions | ICP-MS | Al was detected in infant parenteral nutrition solutions at levels higher than the advised maximum limits | 94 |
| As | Baby food (porridge powder, baby meal), CRM | ICP-MS; AAS | After comparison of several sample preparation procedures, the optimal for determination of iAs and DMA was achieved with a slurry prepared using 3 mol L−1 HCl under heating and ultrasound-assisted agitation, followed by arsine generation, cryogenic trapping and AAS detection. LODs were 0.44 μg kg−1, 0.24 μg kg−1 and 0.16 μg kg−1 for iAs, methylarsonate and DMA, respectively. Besides analysis of a CRM certified for As species in rice, mass balance was performed for all samples and the CRM by comparison between the sum of the species and the total As concentration determined by ICP-MS after microwave-assisted digestion | 109 |
| As | Olive oil (extra virgin) | ETAAS, ICP-MS, SEC-ICP-MS, AEC-ICP-MS | The distribution of As species in extra virgin olive oils from arsenic-endemic areas was assessed using an array of techniques. Oil samples with elevated As levels were identified by ICP-MS after microwave-assisted digestion. From these, fractions of protein-bound and free As were separated by SEC-ICP-MS and further characterised by ETAAS. Additionally, AEC-ICP-MS allowed determination of DMA and AsIII in the proteic fraction | 72 |
| As | Rice | ICP-MS | An investigation of As bio-accessibility and the effect of washing and cooking in 13 different types of rice indicated reduction (3–43%) of As after washing | 143 |
| As | Seafood (shark, shrimp, squid, oyster and scallop), CRM | LC-ICP-MS/MS | After sample extraction with 30 mmol L−1 HNO3, the concentrations of AsB, AsIII, DMA, MMA and AsV were determined by LC-ICP-MS/MS, with (NH4)3PO4 10 mmol L−1 as the mobile phase and conversion of 75As to 75As16O using O2 as the reaction gas. LOQs were 4, 21, 4, 9 and 18 ng g−1 for AsB, AsIII, DMA, MMA and AsV, respectively. Recoveries ranged from 90% to 104%. The influence of culinary treatment on As species was investigated | 118 |
| As | Vegetable oils | HG-AFS | As and Pb were determined simultaneously after vortex-assisted extraction with diluted HNO3. LODs were 0.6 μg kg−1 (As) and 0.4 μg kg−1 (Pb). Recoveries ranged from 84.4% to 105% for both elements. Results of commercial oil samples were in good agreement with those obtained with ICP-MS and microwave digestion | 59 |
| Br | Rice | ICP-MS | Improved LODs (0.004 mg kg−1 and 0.0008 mg kg−1 for Br and I, respectively) were achieved using microwave-induced combustion for sample digestion (up to 1 g) and 50 mmol L−1 NH4OH as the absorbing solution. Recoveries ranged from 98% to 108% and the RSDs were <9 and 11% for Br and I, respectively | 114 |
| Cd | Flavoured yoghurts and cream cheeses | ETAAS | Potential exposure of children from consumption of flavoured yoghurts or cream cheeses was assessed. On average, Cd and Pb levels in flavoured yoghurts were 0.008 mg kg−1 and 0.028 mg kg−1, respectively, and 0.017 mg kg−1 and 0.02 mg kg−1 in cream cheeses | 144 |
| Cd | Rice, CRM | AFS | A procedure based on liquid spray dielectric barrier discharge induced plasma-CVG-AFS achieved an LOD of 0.01 μg L−1 (Cd) and an RSD of 0.8% (n = 5) at 1 μg L−1 Cd | 57 |
| Cd | Wine (white, red, rose and sparkling wines) | ETAAS, ICP-MS | Using DLLME coupled to ETAAS, Cd and Pb were determined with LODs of 0.01 μg L−1 (Cd) and 0.08 μg L−1 (Pb), respectively. The results were comparable to those obtained by ICP-MS after microwave-assisted acid digestion | 145 |
| Cu | Human milk, infant formula, CRM | ICP-OES, FAAS | The determination of Cu, Fe and Zn was achieved without digestion after dilution in ultrapure water, with LOQs of 5 μg L−1, for Cu and Zn, and 10 μg L−1, for Fe. Recoveries ranged from 90% to 102%, from 97% to 103% and from 90% to 94%, for Cu, Fe and Zn, respectively | 146 |
| Cu | Infant formula premixes | LIBS | LIBS was assessed as a fast method to evaluate the content of Cu and Fe in premixes. The optimal results were achieved using PLS regression for calibration | 50 |
| Cu | Oysters (Crassostrea hongkongensis) | nanoSIMS | The cellular and subcellular distributions of Cu and Zn in contaminated oysters were mapped using nano SIMS | 80 |
| Fe | Human milk, infant formula, SRM | ICP-OES, FAAS | See Cu, ref. 146 | 146 |
| Fe | Infant formula premixes | LIBS | See Cu, ref. 50 | 50 |
| Hg | Fish muscle, CRMs | AAS | The mass fractions of total Hg and MeHg in fish muscle were determined using thermal desorption AAS after double liquid–liquid extraction. The LODs were 0.2 μg kg−1 (total Hg) and 3.0 μg kg−1 (MeHg) | 73 |
| Hg | Rice and aquatic plants, CRMs | GC-pyro-AFS | MeHg and Hgi were extracted by closed- vessel microwave-aided digestion, using either acid (6 M HNO3) or alkaline (TMAH) media, followed by ethylation and analysis by GC-pyro-AFS. LODs ranged from 0.7 to 1.0 ng g−1. Recoveries were from 92% to 101% | 55 |
| Hg | Seafood, CRM | CCP-OES | Total Hg was determined in seafood samples digested in HNO3–H2O2, followed by derivatisation with 20% SnCl2 in 15% HCI for analysis by cold vapour CCP-OES. MeHg was separated by double liquid–liquid extraction in 0.6 mol L−1 formic acid followed by photochemical VG. The concentration of Hg2+ was calculated by difference. LODs were 2 and 3 μg kg−1 for MeHg and total Hg, respectively. Recoveries were 101 ± 10%, total Hg, 100 ± 8%, MeHg and 102 ± 13%, Hg2+, respectively, whereas RSDs ranges were 2.4–7.8%, 2.4–11.9% and 3.8–14.0% | 110 |
| I | Cow milk, milk-alternative drinks (soya, almond, coconut, oat, rice, hazelnut and hemp) | ICP-MS | I concentrations in 44 unfortified milk-alternative drinks was low (median: 7.3 μg kg−1) in comparison with 5 conventional cows’ milk samples (median 438 μg kg−1) or 5 organic ones (median 324 μg kg−1). Fortified milk-alternatives were between 266 and 287 μg kg−1 | 112 |
| I | Rice | ICP-MS | See Br, ref. 114 | 114 |
| Mn | Vegetable samples (basil herb, spinach, dill, and cucumber barks), CRM | ICP-OES | Three deep eutectic solvents (choline chloride and either tartaric, oxalic or citric acids) were tested for the quantitative extraction of Mn from vegetable samples, carried out at 95 °C for 2 h. LODs were 0.50, 0.34, and 1.23 μg L−1 for the mixtures of choline chloride with tartaric, oxalic, and citric acid, respectively | 30 |
| Na | Foodstuffs | AAS | A survey of the Na content in foodstuffs included in the sodium reduction regulation of South Africa | 111 |
| Pb | Drinking water | ICP-MS/MS | As an alternative to radiometric techniques, 210Pb was determined by ICP-MS/MS. Two sample preparation approaches were investigated. With sequential, back-extraction CPE a lower LOD (15 fg L−1) and higher extraction rate (80%) were achieved | 40 |
| Pb | Flavoured yoghurts and cream cheeses | ETAAS | See Cd, ref. 144 | 144 |
| Pb | Food samples (infant food, common food and bottled water) | ICP-MS | Lower LOQs (0.6 or 0.9 μg kg−1 (Pb) for liquid or solid samples) were achieved using closed-vessel microwave digestion with 3 mL H2O–3 mL HNO3 and a programmable temperature cyclonic spray chamber | 16 |
| Pb | Vegetable oils | HG-AFS | See As, ref. 59 | 59 |
| Pb | Wine (white, red, rose and sparkling wines) | ETAAS, ICP-MS | See Cd, ref. 145 | 145 |
| Sb | Beverages | ICP-AES | Sb and Sn were determined in beverages after ultrasound-assisted ionic liquid DLLME, with LOD and LOQ of 1.2 and 2.5 ng L−1 (Sb) and 4.0 to 8.3 ng L−1 (Sn), respectively. RSDs better than 2.5% and 4.7% were reported for Sb and Sn, respectively | 147 |
| Sb | Tea leaves and tea infusions, CRM | ETV-ICP-MS | Samples underwent preconcentration and separation of Sb species using dispersive micro-SPE with TiO2 nanofibers, followed by DLLME and analysis by ETV-ICP-MS with APDC as a chemical modifier. The LODs were 0.019 pg mL−1 and 0.025 pg mL−1, for SbIII and SbV, respectively. The RSD at 1.0 ng mL−1 (n = 9) were 5.7% (SbIII) and 6.9% (SbV) | 148 |
| Se | Rice | AE-ICP-MS, RPLC-ICP-MS | Anion exchange and ion pairing RP LC coupled to ICP-MS/MS were compared for Se speciation. The latter, performed using a StableBond C18, with 0.5 mM tetrabutylammonium hydroxide–10 mM CH3COONH4 at pH 5.5 as the mobile phase, achieved the best performances. The LODs were in the range 0.02–0.12 μg L−1. Recoveries of five Se species varied from 75% to 114% and the RSDs were ≤9.4% | 41 |
| Se | Selenised yeast | ICP-MS | The detection of 82Se by ICP-MS allowed to identify the fraction of water soluble low Mr Se-metabolites from selenised yeast, after ultrasound assisted water extraction followed by size exclusion fractionation. 103 selenised species were identified in this fraction by LC-TOF-MS | 74 |
| Se | Torula yeast (Candida utilis) | HILIC-ICP-MS | Selenohomolanthionine was identified as the major Se compound in Torula yeast (Candida utilis), by means of a combination of analytical techniques (HILIC-ICP MS, HILIC-Orbitrap MS and MS–MS fragmentation) | 149 |
| Sn | Beverages | ICP-OES | See Sb, ref. 147 | 147 |
| Ti | Chewing gum | ICP-MS, ICP-MS/MS, spICP-MS | The potential of different measuring modes of spICP-MS for the identification of TiO2 was explored. The LOD for particle size was 26 nm | 43 |
| Tl | Tea leaves and tea infusion, CRM | ETV-ICP-MS | The speciation of TlI and TlIII was achieved using SPE with TiO2 nanofibers to separate Tl from the matrix, followed by elution with diluted HNO3 and further preconcentration and separation by DLLME. The LODs were 0.015 pg mL−1 for TlI and 0.020 pg mL−1 for TlIII. RSDs at 0.10 ng mL−1 were 6.5% and 7.3% (n = 9), respectively | 37 |
| Zn | Human milk, infant formula, SRM | ICP-OES, FAAS | See Cu, ref. 146 | 146 |
| Zn | Oysters (Crassostrea hongkongensis) | nanoSIMS | See Cu, ref. 80 | 80 |
| Zn | Wine | ETAAS, FAAS | Zn in Tannat wine from Uruguay was determined by ETAAS, using direct injection, the alternative wavelength of 307.6 nm and the standard additions method for calibration. The LOQ was 0.10 mg L−1 and repeatability (n = 5) at three concentration levels was <5%. Agreement with the reference method from the Organisation Internationale de la Vigne et du Vin was within 10% | 150 |
| Various | Soil, wine | ICP-MS | Statistical analysis of the content of major and trace elements in soil and wine allowed to identify the geochemical fingerprints of “Prosecco” wine | 151 |
| Various (4) | Water, urine and tea infusions, CRM | FAAS | A method based on liquid phase micro-extraction and micro-sampling FAAS was applied for the determination of Cd, Co, Ni and Pb. The reagents were triethylamine and protonated triethylamine carbonate in the presence of CO2. The metal complexes were extracted into triethylamine by addition of NaOH. With preconcentration factors >100 for all analytes, LODs ranged from 0.24 to 0.76 μg L−1 and the observed RSDs (at 50 μg L−1, n = 10) were between 1.3% and 3.8% | 27 |
| Various (6) | Caviar | ICP-AES | The mass fractions of 6 potentially toxic elements were determined in caviar of Acipenser persicus after acid digestion and on average, found to be 0.01 mg kg−1 for As, Co and Pb, 0.05 mg kg−1 for Cd, 0.28 mg kg−1 for Sn and 1.42 mg kg−1 for Cu | 152 |
| Various (7) | Cocoa powder, chocolate | ICP-MS | The levels of seven elements (As, Cd, Cr, Pb, Sb, Se and V) were determined by ICP-MS in cocoa powder and chocolate after microwave-assisted digestion. The highest levels were observed for As, Cd and Pb | 116 |
| Various (8) | Food (cabbage, bean, beef and fish) | ICP-OES, ICP-MS, CVAAS | The levels of 10 elements (Al, As, Cd, Cr, Cu, Hg, Mn, Pb, Se and Zn) in 120 raw food samples from open markets in two African cities were assessed after microwave-assisted digestion | 153 |
| Various (8) | Wheat | ICP-MS | The bio-accessibility of 8 trace elements (As, Cd, Cr, Cu, Fe, Ni, Pb and Zn) was investigated using sequential leaching from a mini-column of sample, coupled on-line with ICP-MS, by artificial saliva, gastric juice and intestinal juice | 39 |
| Various (9) | Foodstuffs, CRMs | ICP-AES | Nine elements (Ca, Cu, Fe, K, Mg, Mn, Na, P and Zn) were determined after sample digestion with ultrapure 50% (v/v) formic acid on a heating block. Recoveries from the analysis of CRMs (bovine liver, apple leaves and whole milk powder) ranged from 80.7% to 114%, with RSDs <20%. The LODs varied from 0.056 mg kg−1 to 0.06 g 100 g−1 | 29 |
| Various (10) | Almond and peanut powder | ICP-OES | The contents of 10 elements (B, Ca, Cu, Cu, Fe, K, Na, Mg, Sr and Zn) were used as input for multivariate data analysis techniques to identify adulteration of almond powder samples with peanut | 121 |
| Various (10) | Wine | LIBS | 2 mL of wine dried on a metallic surface provided a suitable sample preparation method to determine 10 elements (B, Ba, Ca, Cu, Fe, K, Li, Mg, Mn, Na, P, Pb, Rb, Si, Sr, Ti and Zn) by LIBS, with LODs ranging from 0.1 to 1.5 mg L−1 | 53 |
| Various (12) | Milk, milk products, infant formula, and adult/pediatric nutritional formula, SRM | ICP-MS, ICP-OES | The results of a collaborative study of an AOAC Official method for the determination of 12 elements (Ca, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, P, Se and Zn) by ICP-MS after microwave-aided digestion were reported and compared to those obtained by ICP-OES | 15 |
| Various (17) | Flour (from cassava, corn and wheat), CRMs | ICP-MS, ICP-OES | 17 elements (Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Ni, P, S, Sb, Sr and Zn) were determined in various flour types after microwave-assisted digestion. Analysis of CRMs provided values between 82 ± 3% (Cr) and 108 ± 10% (Fe) of the certified values. RSDs (n = 3) were lower than 9% for all elements, except for Cd (14%). Multivariate data analysis techniques were applied to evaluate categorisation based on the elemental profile | 113 |
| Various (17) | Potatoes (Solanum tuberosum) | ICP-MS | 17 trace elements were determined in potatoes from 51 plantations to exclude potential environmental contamination | 154 |
| Various (REEs) | Rabbit meat | ICP-MS | The determination of element composition, including REEs, enabled discrimination of wild rabbit from non-wild rabbit meat | 120 |
8.2 Single and multielement applications in food and beverages
A proposed alkali dilution preparation method for the determination, of heavy and essential elements in human milk by ISP-MS was directly compared with a standard microwave-assisted acid (HNO3) digestion by Levi et al.23 Samples (0.2–0.3 g) were diluted 1 + 24–35 with 2% butanol, 0.05% EDTA, 0.05% Triton X-100, 1% NH4OH, sonicated (5 min), centrifuged at 2000 rpm (5 min) then analysed immediately by ICP-MS. For comparison, samples (1 g) were mixed with HNO3 (2 g, 65% w/w) and H2O (3 g) and digested at 250 °C and 40 bar for 30 min then diluted 1 + 9. A large number (n = 237) of human milk samples, from Salta, Argentina, were subjected to both methodologies and results compared using Bland–Altman difference plots and Spearman’s correlation. For Ca, Fe and Zn the acid method is preferred due to the propensity for these elements to precipitate in alkaline conditions. The alkali method is favoured for Cd and I largely because of losses due to the volatility of HI and I2, which occurs more easily at low pH. For the remainder (B, Li, Mg, Na and Se) both methods are suitable although the short analysis time and higher precision would favour the use of the alkali method.
Cama-Moncunill et al.49 assessed the suitability of LIBS for quality control of Cu and Fe in infant formula. As quantitation using LIBS spectra is affected by several issues, the authors tested three matrix-matched calibration approaches (simple-linear regression, multi-linear regression and PLS regression) to enhance precision and accuracy in a series of formula preparations containing differing proportions of premix and lactose. Only PLS was able to provide good predictive power for quantitation. Loadings of the model indicated that not only emission intensities of Cu, Fe and Zn were important but also C, Ca, K and Na, indicating matrix constituents were also important in building the quantitative calibration. That N, O and H also played a role implicated the surrounding air as having an involvement in the accuracy of the model. This was confirmed by comparing results from 5 layers and it was recommended to discard surface measurements.
Determination of Br and I in rice following microwave-induced combustion gave low LODs (0.004 and 0.0008 mg kg−1, respectively) when determined by ICP-MS.114 These levels were obtained using a 1 g sample mass and an optimised absorbing solution (50 mmol L−1 NH4OH). The sample was wrapped in PE film, placed on a filter paper disc moistened with NH4NO3 (6 mol L−1, 50 μL) supported by a quartz holder and placed in the closed quartz vessel containing the absorbing solution (6 mL) which was pressurised with O2 prior to heating. The recoveries observed for both analytes ranged from 94 to 97% with RSDs <13%. Most samples presented Br concentrations in the range 0.32–2.2 mg kg−1 apart from two basmati rice samples from the Himalayas and USA (24.9 and 55.7 mg kg−1, respectively) and one brown rice sample from USA (9.6 mg kg−1). Concentrations of I were in the range 0.003–0.031 mg kg−1, with no high values concomitant with those seen for Br.
Little knowledge is available on Te in food but is expected to be similar in bioaccumulation and biosynthesis to S and Se. Berenguel et al.115 were the first to study Te in Brazil nuts (Bertholletia excelsa) by ICP-MS for total Te and its bioaccessibility. A microwave-assisted digestion was used (200 mg ground sample) with HNO3 (68%, 3 mL) and H2O2 (30% w/v, 2 mL) in a three-step program: 330 W, 8 min; 590 W, 5 min; 720 W, 40 min and then diluted to 5 mL. The unified bioaccessibility method, developed by the Bioaccessibility Research Group of Europe, was used to produce salivary, gastrointestinal and gastric fractions for ICP-MS determination. Quantification was achieved using 128Te (31.69% abundance) to avoid isobaric interferences of Ba and Xe; external calibration was applied and yielded an LOQ of 0.04 μg L−1. Samples from two batches of nuts purchased in São Paulo, Brazil gave total Te as 4.15 ng g−1; 32% was bioaccessible through gastric digestion and 30% from gastrointestinal digestion.
Widely consumed, soy sauce is difficult to analyse because of a highly saline matrix and highly condensed phase which lends itself to analysis by TXRF even with no prior application development.65 A digestion was performed (1 g sample) with HNO3 (65%, 1.5 mL) and H2O2 (40%, 0.5 mL) in a sealed vial heated to 130 °C for 1 h prior to drying an aliquot (8 μL) on a siliconised quartz reflector at 90 °C. Data were acquired over 300 s in a benchtop TXRF spectrometer equipped with a monochromatic X-ray source (Mo-Kα, 17.4 keV) at 40 kV, 15 mA and a 25 mm2 Si Drift Detector. Recovery was verified for all analytes (Ba, Br, Ca, Co, Cr, Cu, Ga, Fe, K, Mn, Ni, P, Pb, Rb, S, Sr, Ti, V, Zn) by spiking into each of six samples analysed, and falling within the range 90–110%. The digestion reduced the organic background signal (4–14 keV) by 30%, and the Cl signal (2.6 keV) by a factor of 10. The LODs of toxicologically important elements was quoted as 0.5 mg kg−1 and deemed suitable for health risk assessment. Comparison, by paired t-test, of concentrations of Cu, Fe, Mn, Rb, Sr and Zn, measured using ICP-MS following a 500-fold dilution, showed there is no statistical difference at the 95% confidence interval. A simple dilution (1 + 4) can also be employed without digestion if the XRF experiment is run in the grazing incidence mode although this gives a −5% bias. Mean concentrations of the six soy sauces analysed were: Br: 4.1; Ca: 117; Cl: 3059; Cu: 0.26; Fe: 18; K: 2511; Mn: 6; Ni: 9; P: 370; Rb: 2.2; S: 522; Sr: 3.3; Zn: 5.6 mg kg−1.
A method for cocoa and chocolate analysis, capable of attaining the levels of sensitivity required by the EU for Cd and Pb in foodstuffs, was developed using ICP-MS with He and H2 as reactant gases.116 Samples (1 g) were prepared with microwave-assisted acid digestion (HNO3, 60%, 3 mL; H2O, 5 mL) and the analysis included other elements in addition to Cd and Pb. Although the LOQs for Cd and Pb were not directly reported, their quoted values for Cd, Cr and Pb were more than 10 times lower than for AA, although the LOQs of all metal analysed fell between 5.22 μg kg−1 (Sb) and 9.55 μg kg−1 (Se). Median concentrations (mg kg−1) for cocoa powders (n = 35) produced in Italy were As: 0.026 ± 0.003; Cd: 0.159 ± 0.02; Cr: 1.315 ± 0.147; Pb: 0.417 ± 0.032; Sb: 0.383 ± 0.041; Se: 0.076 ± 0.007; V: 0.196 ± 0.022. Concentrations of these elements in chocolate samples (n = 105) increased according the proportion of dry cocoa used. The EU limits for Cd and Pb (0.3 and 1.0 mg kg−1) were exceeded in at least one sample. An almost identical survey was carried on Cd and Pb by the US FDA.117 Samples (0.5 g), ground when frozen to −30 °C, were prepared by microwave-assisted digestion (HNO3, 67%, 5 mL; H2O2, 30%, 5 mL) with a ramp to 250 °C over 30 min then held at temperature for 15 min before HCl (10%, 2.5 mL) was added once the sample cooled. Samples were analysed by ICP-MS achieving LOQs of 3.7 and 10.0 μg kg−1 for Cd and Pb and recoveries of SRM 2384 Baking Chocolate were acceptable. The Cd and Pb concentrations of 144 chocolate product samples purchased from retail shops in Maryland, USA or online ranged from 0.004 to 3.15 mg kg−1 and <LOD to 0.38 mg kg−1, respectively. The data also confirmed a geographic variation, with higher concentrations of Cd and Pb in products originating from Latin America compared with those from Africa, particularly for cocoa, which also had the highest Cd concentrations relative to the other chocolate products.
The consumption of caviar is deemed safe 119 with low levels of heavy metals giving a health risk index <1, despite the discharge of hazardous chemicals into the marine ecosystems of the Caspian Sea, where residue analysis of pollutants in seafoods is recommended. Roe from wild Persian sturgeon (Acipenser persicus) was collected, washed, dried and ground and prepared for determination of As, Cd, Co, Cu, Pb and Sn by ICP-OES with microwave-assisted acid digestion (1.5 mL HNO3, 0.1 g sample). The mean concentrations (mg kg−1) were given as As: 0.01; Cd: 0.05; Co: 0.01; Cu: 1.42; Pb: 0.01; Sn: 0.28 which are significantly lower than the adverse levels for the human consumption. The authors concluded that consumption of caviar posed no significant health risk for adults and children. While this appears to be good news, there may a problem with the data in that the quoted LOQs appear to be too high to reliably measure these low concentrations.
9 Abbreviations
| AAS | Atomic absorption spectrometry |
| ADPC | Ammonium pyrrolidine dithiocarbamate |
| AEC | Anion exchange chromatography |
| AF | Atomic fluorescence |
| AFS | Atomic fluorescence spectrometry |
| AsB | Arsenobetaine |
| ASU | Atomic Spectrometry Update |
| CCD | Charge coupled device |
| CPE | Cloud point extraction |
| CRM | Certified reference material |
| CV | Cold vapour |
| CVG | Chemical vapour generation |
| DLLME | Dispersive liquid–liquid microextraction |
| DMA | Dimethylarsenic |
| DMF | Dimethylformamide |
| DMSO | Dimethylsulfoxide |
| DMSPE | Dispersive micro-solid phase extraction |
| dw | Dry weight |
| EDTA | Ethylenediamine tetraacetic acid |
| EDXRF | Energy dispersive X-ray diffraction |
| EF | Enrichment factor |
| EPA | Environmental Protection Agency |
| FETAAS | Electrothermal atomic absorption spectrometry |
| EtOH | Ethanol |
| ETV | Electrothermal vaporisation |
| EU | European Union |
| EXAFS | Extended X-ray absorption fine structure |
| FAAS | Flame atomic absorption spectrometry |
| FTIR | Fourier transform infra-red |
| GSH | Glutathione |
| HG | Hydride generation |
| HPLC | High performance liquid chromatography |
| HR | High resolution |
| IAEA | International Atomic Energy Authority |
| iAs | Inorganic arsenic |
| IC | Ion chromatography |
| ICP-AES | Inductively coupled plasma atomic emission spectrometry |
| ICP-MS | Inductively coupled plasma mass spectrometry |
| ICP-OES | Inductively coupled plasma optical emission spectrometry |
| ICP-QMS | ICP-quadupole MS |
| ID | Isotope dilution |
| iHg | Inorganic mercury |
| IL | Ionic liquid |
| IPA | Isopropyl alcohol |
| LA | Laser ablation |
| LC | Liquid chromatography |
| LDA | Linear discriminant analysis |
| LIBS | Laser induced breakdown spectroscopy |
| LOD | Limit of detection |
| LOQ | Limit of quantification |
| LPME | Liquid phase micro-extraction |
| MC | Multicollector |
| MeHg | Methyl mercury |
| MeOH | Methanol |
| MMA | Monomethylarsonic acid |
| MPT | Microwave plasma torch |
| MS | Mass spectrometry |
| NIST | National Institute of Standards and Technology |
| NP | Nanoparticle |
| OES | Optical emission spectrometry |
| PCA | Principal component analysis |
| PEG | Polyethylene glycol |
| PEEK | Polyetheretherketone |
| PLSR | Partial least squares regression |
| PN | Parenteral nutrition |
| PTFE | Poly(tetrafluoroethylene) |
| PTWI | Provisional tolerable weekly intake |
| ICP-QMS | Quadupole-ICP-MS |
| QQQ | Triple quadrupole |
| REE | Rare earth elements |
| RM | Reference material |
| RSD | Relative standard deviation |
| SD | Standard deviation of mean |
| SEM | Scanning electron microscopy |
| SEC | Size exclusion chromatography |
| SF | Sector field |
| SPE | Solid phase extraction |
| spICP-MS | Single particle ICP-MS |
| SRM | Standard reference material |
| SR-XRF | Synchrotron radiation X-ray fluorescence |
| STIM | Scanning transmission ion microscopy |
| TEM | Transmission electron microscopy |
| THF | Tetrahydrofuran |
| TIMS | Thermal ionization mass spectrometry |
| TOF | Time-of-flight |
| TPN | Total parenteral nutrition |
| TRIS | Tris(hydroxymethyl)aminomethane |
| TXRF | Total reflexion XRF |
| UPLC | Ultra high performance liquid chromatography |
| UV | Ultraviolet |
| VG | Vapour generation |
| WHO | World Health Authority |
| ww | Wet weight |
| XRD | X-ray diffraction |
| XRF | X-ray fluorescence |
| XRPD | X-ray powder diffraction |
10 Conflicts of interest
There are no conflicts to declare.11 References
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