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Dried blood spots (DBS) are well established in clinical laboratory medicine and are used to screen newborn babies for a large number of metabolomic disorders. More than 50 years ago, early attempts to analyze DBS for Pb content identified several major limitations, which continued to be reported on for decades, including the unknown volume of blood deposited, the tendency of red blood cells to accumulate at the periphery of the spot and contamination errors. The historical literature on DBS blood Pb measurement is replete with competing claims for success as well as reports on the limitations for screening and diagnostic purposes. The range of spectroscopic techniques used to measure Pb in DBS includes atomic absorption spectrometry and inorganic mass spectrometry. There is a broad consensus that the analysis of archived DBS samples from newborn screening programs suffers from sporadic background contamination for many elements, the magnitude of which makes such samples unreliable for biomonitoring studies. Yet, the introduction of inorganic mass spectrometry into clinical laboratories provides the potential for multielement analysis of DBS. For some elements that are present at relatively high concentrations, such as Ca, Cs, Cu, Fe, K, Mg, Na, P, Rb, S and Zn, reasonable data may be feasible on archived DBS that are stored appropriately. However, for biomonitoring studies, analysis of DBS for many trace elements is fraught with contamination errors, inadequate limits of detection and a lack of well validated field-based studies. This is particularly true for Pb, Cd and Hg, for which only crude screening for acutely elevated levels can be useful. But for other elements such as Cu, Zn, Se, there may well be some value in using prospectively collected DBS to obtain population-based data. More recent developments with volumetric absorptive devices and microfluidic devices address some of the limitations inherent in DBS analysis and hold more promise for achieving reliable measurements of elemental content, but more work is needed to characterize background contamination, especially under real-world field conditions. In conjunction with well established capillary blood collection devices, these new technologies may provide better approaches to obtaining reliable environmental exposure information in the future for prospectively collected samples in population-based studies. [ABSTRACT FROM AUTHOR]

Keratinized tissues comprise a diverse family of materials that includes hair, nails, horns, and hooves. Because of their convenience for collection, affinity for binding some trace elements, and the potential to provide information about historical exposure, hair and nails have been used to assess population exposure to toxic metals and metalloids. Previous studies, however, report a lack of harmonization and poor reliability among commercial laboratories performing trace element analysis of hair. In this interlaboratory study, four keratinized reference materials (RMs) were produced from caprine horns obtained post-mortem from Pb-dosed goats. The homogenized RMs were circulated to laboratories that conduct trace element analysis of keratinized tissues to assess interlaboratory harmonization. Sources of variability in the analytical methods used by participants were investigated. Results were obtained from 21 participant laboratories for a total of 44 elements. Good interlaboratory agreement was found for the majority of elements typically measured using ICP-MS following acid digestion. However, for Al, Cr, Hg, Mo, Ni and V, there was a poor consensus, caused in part by differences in correcting for spectral interferences. Measurements for Hg were inconsistent, which suggests a need for increased efforts to achieve better harmonization. Sample mass for acid digestion was negatively correlated (p = 0.02) with reported Pb content. Higher digestion temperatures were correlated with increased Mn recovery. A limited quantity of four well-characterized caprine horn RMs were produced as a result of this study and serve as a resource for future harmonization efforts. [ABSTRACT FROM AUTHOR]

Follicular fluid (FF), which is the fluid that envelops the developing oocyte (egg cell) in the ovary, can be analyzed to assess trace element content as well as to determine potential exposure to toxic elements in women seeking in vitro fertilization (IVF) treatment. Such measurements may be useful in establishing associations with potential adverse effects on oocyte viability and subsequent pregnancy outcomes. The principal goal of this study was to leverage the next generation of inorganic mass spectrometry based on ICP-MS/MS to address the numerous analytical challenges of (ultra-)trace element analysis of human FF specimens. Ultra-trace element measurements are defined by the Clinical Laboratory Standards Institute as fluid concentrations below 10 μg L−1 or tissue mass fractions below 1 μg g−1. Stringent pre-analytical procedures were developed to minimize exogenous contamination during FF specimen collection and storage in a prospective study of 56 women seeking IVF treatment. ICP-MS/MS instrumental parameters were carefully optimized, and the method validated for 11 biologically important elements that included 4 at trace levels (Cu, Se, Sr, and Zn) and 7 at ultra-trace levels (As, Cd, Co, Mo, Mn, Hg, and Pb). Method limits of detection (LODs) for ultra-trace elements varied from 5.6 ng L−1 for Cd to 0.11 μg L−1 for Mo. A total of 197 human FF specimens were analyzed using the proposed ICP-MS/MS method with 84% of specimens detectable for Pb and 100% detectable for Co, Cu, Mn, Mo, Sr, and Zn. The method based on ICP-MS/MS was compared to a previous method developed for FF using SF-ICP-MS. [ABSTRACT FROM AUTHOR]

The arsenic content of dried baby shrimp (Acetes sp.) was investigated as part of an independent field study of human exposure to toxic metals/metalloids among the ethnic Chinese community located in Upstate New York. The dried baby shrimp were analyzed in a home environment using a portable X-Ray Fluorescence (XRF) instrument based on monochromatic excitation. Study participants had obtained their dried baby shrimp either from a local Chinese market or prepared them at home. The shrimp are typically between 10–20 mm in size and are consumed whole, without separating the tail from the head. Elevated levels of As were detected using portable XRF, ranging between 5–30 μg g−1. Shrimp samples were taken to the Cornell High Energy Synchrotron Source (CHESS) for Synchrotron Radiation μXRF (SR-μXRF) elemental mapping using a 384-pixel Maia detector system. The Maia detector provided high resolution trace element images for As, Ca, and Br, (among others) and showed localized accumulation of As within the shrimp's cephalothorax (head), and various abdominal segments. As quantification by SR-μXRF was performed using a lobster hepatopancreas reference material pellet (NRC-CNRC TORT-2), with results in good agreement with both portable XRF and ICP-MS. Additional As characterization using μX-ray Absorption Near Edge Spectroscopy (μXANES) with the Maia XRF detector at CHESS identified arsenobetaine and/or arsenocholine as the possible As species present. Further arsenic speciation analysis by LC-ICP-MS/MS confirmed that the majority of As (＞95%) is present as the largely non-toxic arsenobetaine species with trace amounts of arsenocholine, methylated As and inorganic As species detected. [ABSTRACT FROM AUTHOR]

International standards for the recognition of the competence of testing laboratories require that measurement results should be traceable to a conventionally agreed reference. This should be achieved by appropriate calibration of equipment and method validation involving analysis of certified reference materials (CRM). However, these are costly and for many analytical procedures, few are available. Participation in external quality assessment schemes (EQAS) may provide a mean to support the laboratory traceability statement, if the values assigned to test samples are traceable to a stated reference. Values may be assigned to EQAS test samples by a variety of techniques but there has been no direct comparison of results obtained when these procedures are applied to the same samples. In this study, traceable values for Cu, Se and Zn concentrations were assigned to three batches of EQAS serum samples, by analysis by expert laboratories together with CRMs, and compared with those obtained by three other of the approaches described in ISO 13528; analysis by a definitive method (ID-ICP-MS); determination of robust consensus mean from the results of expert laboratories; robust consensus mean of results from EQAS participants. The assigned values (µmol L-1) ± expanded uncertainty (%) for the low, medium and high pools obtained by ID-ICP-MS were: Cu 13.37 ± 1.2, 21.03 ± 1.8, 28.73 ± 1.2; Se 0.74 ± 3.5, 1.51 ± 3.4, 3.11 ± 3.6; Zn 9.69 ± 4.9, 22.52 ± 1.5, 30.85 ± 3.8. Concentrations determined using the three other approaches were similar but the uncertainties increased as the methodologies became increasingly less rigorous. [ABSTRACT FROM AUTHOR]

In biomonitoring studies, the very low levels of uranium [U] found in urine and the complexity of the urine matrix present challenges for accurate isotope ratio determination. The principal goals of this study were to evaluate current interlaboratory performance and measurement reproducibility for determining [U] and uranium isotope ratios in human urine, and to produce an archive of well-characterized urine reference materials for future method validation and quality control purposes. Six stabilized pools of urine were prepared following the same protocol that is used to prepare materials for the New York State Department of Health (NYSDOH) Proficiency Testing (PT) Program. The candidate reference materials were characterized by their [U] content, isotopic ratios, as well as for homogeneity, and stability. The interlaboratory study design was modeled on the PT program for trace elements in human urine operated by the NYSDOH's Wadsworth Center. Among the nine laboratories that returned results, sample preparation methodologies included simple dilution, acid digestion, column extraction, or a combination of these techniques. For [U] determination, four laboratories used SF-ICP-MS and five used Q-ICP-MS, whereas, for isotope ratios, five used SF-ICP-MS and four Q-ICP-MS. Sample introduction was achieved using either desolvation-nebulization systems or a nebulizer and spray chamber (ambient temperature or Peltier-cooled). Certified reference materials were used by six laboratories to validate [U], isotope ratios, or both. In general for values of [U] > 5 ng L-1, the assigned target values are in good agreement with predicted values and the standard uncertainties are relatively small. For 235U/238U, there was generally good agreement between the target and predicted values, however the relative standard uncertainties for isotope measurements were higher than for [U]. For the minor isotope ratios 234U/238U and 236U/238U, there was generally poor agreement between target and predicted values and the standard uncertainties were also relatively high. These results suggest that accurate and precise measurements of [U] in urine can be achieved using a wide range of ICP-MS instrument types and methodologies. In contrast, measurement of uranium isotope ratios in urine is more strongly dependent on instrumentation and analytical methodology. [ABSTRACT FROM AUTHOR]

As interest increases in human biomonitoring for exposure to manganese (Mn) via analysis of bone and teeth, there is a growing need for calcified reference materials (RMs) certified for Mn content. Here, several existing calcified RMs and synthesized hydroxyapatite (HA) RMs were digested with acid and subsequently analyzed for Mn by graphite furnace atomic absorption spectrometry (GFAAS) and dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS). Based on GFAAS and DRC-ICP-MS results, mean values and expanded uncertainties were assigned to four New York State (NYS) Bone RMs (05-01 through 05-04), and six synthesized HA standards. Consensus values and expanded uncertainties for Mn content were assigned to NIST SRM 1400 Bone Ash (16.5 ± 2.3 µg g-1) and NIST SRM 1486 Bone Meal (1.1 ± 0.5 µg g-1) by combining GFAAS and DRC-ICP-MS results with literature values. These powdered RMs were also prepared for solid sampling techniques by pressing them into pellets for subsequent analysis by laser ablation (LA-) ICP-MS. The "dilution" effect from adding a chemical binder to the pellets was quantified by both GFAAS and DRC-ICP-MS, and the decrease in Mn mass fraction was found to be proportional to the amount of binder added. The distribution of Mn across the RM pellets was determined by LA-ICP-MS to assess homogeneity and suitability for use as solid standards. The bone RMs were more heterogeneous than the synthesized HA RMs, but the latter may be a less optimal matrix-match due to the absence of organic material. [ABSTRACT FROM AUTHOR]

Determination of uranium isotopes in urine is critical for distinguishing between exposure to natural and anthropogenic sources of uranium. In biomonitoring, the extremely low levels of total uranium [U] present in urine and the complexity of the urine matrix present challenges to accurate isotope ratio determination. We have validated a method for measurement of 234U/238U, 235U/238U and 236U/238U in small-volume, random urine samples at occupational exposure levels, as well as for measurement of 235U/238U at biomonitoring levels. The method has been developed to detect exposure to mixtures of enriched and depleted uranium (DU) among former workers and nearby residents of the NL Industries factory in Colonie, NY, USA. Validation experiments employing solid phase extraction followed by SF-ICP-MS analysis were performed on base urine spiked with isotopic certified reference materials, isotopically depleted urine quality control materials, and natural uranium urine pools. Our results show that extraction with UTEVA resin yields lower blank levels than with TRU resin, and that double washing of the UTEVA resin columns results in further lowering of the blank. At occupational exposure levels ([U] = 50 ng L−1), 234U/238U, 235U/238U, and 236U/238U can be quantified in 1 mL of urine containing 3% DU with relative precisions (1s) of 10%, 0.4%, and 18%, respectively. For urine containing 75% DU and [U] = 50 ng L−1, the relative precision (1s) of 236U/238U is improved to ＜3%. At biomonitoring levels ([U] = 5 ng L−1), by increasing the urine volume to 4 mL, 234U/238U and 235U/238U can be quantified with relative precisions (1s) of 19% and 0.5%, respectively, whereas 236U/238U cannot be detected. By further increasing urine volume to 8 mL, comparable levels of isotope ratio precision are possible at [U] as low as 1 ng L−1. [ABSTRACT FROM AUTHOR]

Analysis of human urine is commonly used in biomonitoring studies to assess exposure to essential (e.g., Cu, Zn, Se) and non-essential (Pb, Cd, Pt) trace elements. These data are also used in epidemiological studies to evaluate potential associations between trace element exposure and various health outcomes within a population. Today most trace element analyses are typically performed using quadrupole-based inductively coupled plasma mass spectrometry (Q-ICP-MS). However, there is always the potential for spectral interferences with Q-ICP-MS instrumentation, especially when analyzing human specimens that may contain medications and other exogenous substances. Moreover, such xenobiotics may be unknown to the investigators. In a recent study focusing on environmental exposures and endometriosis: Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO Study), urine specimens (n = 619) were collected from participating women upon enrollment into the study or prior to surgery or pelvic magnetic resonance imaging (MRI), and analyzed for 21 trace elements by Q-ICP-MS. Here we report on some anomalous results observed for Se and Pt with elevated concentrations up to several orders of magnitude greater than what might be expected based on established reference intervals. Further investigations using Sector Field (SF-) ICP-MS instrumentation led to identification of doubly charged and polyatomic gadolinium (Gd) species traced to a Gd-based contrast agent that was administered to some subjects just prior to urine collection. Specifically, interferences from Gd2+ and several minor polyatomics were identified as interferences on all of the major isotopes of Se including 74Se, 76Se, 77Se, 78Se, 80Se, and 82Se. While trace amounts of Pt were present in the urine, a number of Gd-containing polyatomic species were also evident as major interferences on all isotopes of Pt (190Pt, 192Pt, 194Pt, 195Pt, 196Pt, and 198Pt), including Gd-chlorides, Gd-argides, and Gd-oxides. These observations underscore the importance of considering potential isobaric interferences when interpreting unusual trace element results for clinical specimens. [ABSTRACT FROM AUTHOR]

Biomonitoring for manganese (Mn) exposure is important due to its potential to cause adverse health effects. In this study, we investigate how different sample preparation methods (dilution, digestion), calibration protocols (aqueous, blood-based, standard additions), and instrumental techniques affect Mn method bias and analytical imprecision. The techniques used included graphite furnace atomic absorption spectrometry (GFAAS), dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS), and sector field (SF-) ICP-MS. We analyzed NIST SRM 1643e Trace Elements in Water and SRM 1598a Inorganic Constituents in Animal Serum (both certified for Mn), and SRM 955c Toxic Metals in Caprine Blood – Level 1 (not certified for Mn). Various matrix effects in ICP-MS produced inaccurate results for SRM 1643e and discrepant results for SRM 955c. In the absence of a certified value for Mn in SRM 955c, we assigned a “consensus” value by combining data from the New York State Department of Health (NYS), the Centers for Disease Control and Prevention (CDC) and the Centre de toxicologie du Québec (CTQ). With this interlaboratory approach, we established an “all-lab” consensus value of 16.3 ± 0.8 μg L−1 based on data from DRC-ICP-MS with dilution sample preparation and blood-based calibration. We also assigned an “all-method” consensus value of 16.3 ± 0.9 μg L−1 based on GFAAS and SF-ICP-MS data from the NYS lab and the DRC-ICP-MS all-lab consensus value. Although the expanded uncertainty (U) calculated for the consensus values may not fully account for all sources of uncertainty, it does show the relative variation that might be expected from one study to the next for the determination of Mn in blood. [ABSTRACT FROM AUTHOR]

Little information is available in the literature regarding trace element analysis of human follicular fluid. Most peer-reviewed publications offer few details about sample preparation, method development, or method validation. We have attempted to fill this gap in current knowledge by providing comprehensive details of our method development and validation process for the measurement of 24 trace elements (As, Ba, Be, Cd, Co, Cr, Cs, Cu, Hg, Mo, Mg, Mn, Pb, Pt, Rb, Se, Sb, Sn, Sr, Tl, U, V, W, Zn) in follicular fluid. A number of different sample preparation procedures were explored, with a goal of optimizing method detection limits (MDLs), for both quadrupole-inductively coupled plasma-mass spectrometry (Q-ICP-MS) and sector field (SF)-ICP-MS. Human follicular fluid samples (n = 72) were obtained from 64 women undergoing in vitro fertilization (IVF) treatment, and were successfully analyzed for 24 trace elements using SF-ICP-MS. [ABSTRACT FROM AUTHOR]

109Cd-based K-shell X-ray fluorescence spectrometry (hereafter, for brevity, XRF) is used, often in epidemiological studies, to perform non-invasive, in vivo measurements of lead in bone. We conducted the first interlaboratory study of XRF via the circulation of nine goat tibiæ in which the mean lead value ranged from 4.0 μg g−1 to 55.3 μg g−1 bone mineral. The test tibiæ were subsequently analyzed via nitric acid digestion followed by lead determination by inductively coupled plasma mass spectrometry (ICP-MS) – along with certified reference materials for bone lead – thus providing measurement traceability to SI units. Analysis of dried bone for lead via nitric acid digestion and ICP-MS yields mass fraction data in units of μg g−1 dry weight. The mean bone lead value based on ICP-MS analysis ranged from 1.8 μg g−1 to 35.8 μg g−1 dry weight. For comparison purposes, XRF-measured Pb values (μg g−1 bone mineral) were converted into the ICP-MS-measured units (μg g−1dry weight bone) by multiplying the former by the average ash fraction from the nine tibiæ. Eight of the XRF systems did not yield a significant bias for any of the nine tibiæ; one system was biased for one of the tibiæ; two systems were biased for two tibiæ; one system was biased for four tibiæ; two systems (813-1 and 804-2) were biased for five tibiæ and one system (801-1) was biased for six of the nine tibiæ. Average bias for the systems (under those particular operating conditions) that were biased for the majority of samples ranged from −2.6 μg g−1 (−15.7%) to 5.1 μg g−1 (30.7%) dry weight bone. All participants now have the ICP-MS data, allowing any corrective actions deemed necessary to be implemented. The ICP-MS data, however, indicated that the lead mass fraction varied considerably with the sampling location within the tibiæ, to the extent of exceeding XRF variability for the higher lead values. Material heterogeneity is an unavoidable reality of measuring lead in bone. [ABSTRACT FROM AUTHOR]

A limited interlaboratory study for arsenic speciation analysis of whole blood was conducted in conjunction with the New York State Department of Health's (NYS DOH's) proficiency testing (PT) program for total arsenic in whole blood. Four laboratories were able to report values for up to five arsenic species in blood materials representing typical environmental concentrations. The arsenic species were very challenging to measure, due to the low concentrations (＜MDL―9.5 μg L−1). For most arsenic species, good agreement among the participants was observed and the consensus mean values obtained can be considered as the assigned target values for use as quality assurance materials in future analyses. [ABSTRACT FROM AUTHOR]

Measurements of Mn in blood and urine are used in biomonitoring studies as biomarkers of exposure. We compared methods for determining Mn, including graphite furnace atomic absorption spectrometry (GFAAS), quadrupole-based inductively coupled plasma mass spectrometry (Q-ICP-MS) (standard and dynamic reaction cell (DRC) mode), and sector field (SF-) ICP-MS. We investigated polyatomic interferences in ICP-MS that can affect Mn measurements in blood and urine matrices, especially at concentrations associated with biomonitoring studies. Method detection limits (3SD) for blood (and urine) Mn were 1.5 (2.1) µg L−1for GFAAS, 0.6 (0.5) µg L−1for SF-ICP-MS, 1.0 (0.5) µg L−1for DRC-ICP-MS and 6.4 (0.6) µg L−1for Q-ICP-MS operated in standard mode. Method reproducibility for blood (22 µg L−1Mn) and urine matrices (9 µg L−1Mn) was found to be between 3 and 4% RSD for all methods, except for blood Mn by Q-ICP-MS (11% RSD) and urine Mn by GFAAS (7% RSD). Accuracy was assessed using various reference materials. Careful optimization of the DRC mode is required with blood because, in addition to polyatomic interferences, a large amount of Fe causes spectral overlap on Mn. GFAAS, DRC-ICP-MS and SF-ICP-MS methods show good agreement for Mn in urine and blood across the clinical range studied and, when properly optimized, are suitable for monitoring Mn in blood and urine. In contrast, Q-ICP-MS in standard mode exhibits a positive bias of ∼1 µg L−1in urine and ∼4 µg L−1in blood with respect to the other three methods investigated. The implications of this work are important when biomonitoring studies are compared and reference ranges are established. [ABSTRACT FROM AUTHOR]

Lanthanide elements are finding increasing use in industrial, technological, and medical applications, due to their unique magnetic, optic, and catalytic properties. Consequently, the risk of human exposure to these nonessential elements is rising, and the ability to measure the lanthanides in human tissues and body fluids is gaining in importance. In this study, the concentrations of naturally occurring lanthanide elements, as well as Sc, were measured in human placental tissues, consisting of ∼160 samples each of placenta body, membrane, and umbilical cord, for evaluation of possible maternal and fetal exposure to these metals. Measurements were conducted using ICP-MS instrumentation coupled to a membrane desolvation introduction system, in order to enhance sensitivity for these elements, as well as to decrease oxide formation. Method detection limits (MDLs) ranged from 0.3 ng g−1to 4 ng g−1. Method validation entailed the use of a mussel tissue reference material (RM) certified for most of the analytes of interest, spike recovery experiments and, for some analytes, a caprine liver secondary RM. Heavier lanthanides (Eu–Lu) were not detectable in most placental tissues. Lighter lanthanides (La–Sm) were detected in the ng g−1range. The placenta body accumulated the greatest concentrations of lanthanides. Lanthanide concentrations in placenta appeared to follow a pattern similar to that found in the Earth's crust, indicating natural human exposure to these analytes. [ABSTRACT FROM AUTHOR]

A method was developed to quantify five arsenic species (As(iii), As(v), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB)) in whole blood, using liquid chromatography (LC) coupled with inductively coupled plasma mass spectrometry (ICP-MS). The method can be used for routine monitoring of arsenic species in whole blood as well as in urine, but with different sample preparation. Whole blood was diluted 1 + 4 with reagents containing 3 mM HgCl2, which prevents As(iii) from binding to the LC column. The diluted blood was subjected to ultrafiltration so as to remove molecules larger than 3,000 Daltons. Analysis was completed within 12 min, for the determination of arsenic species in whole blood, and within 11 min in urine; the method detection limit is < 0.3 μg L−1for each arsenic species. The sum of arsenic species measured by the proposed method agreed well with assigned values for total arsenic in whole blood and urine reference materials, and in archived proficiency testing materials. Some urine reference materials provided additional information on the arsenic species present, and our testing results agreed well with the documented values. [ABSTRACT FROM AUTHOR]