The development and implementation of quality assurance programs to support nutritional measurements.

The National Institute of Standards and Technology administers quality assurance programs devoted to improving measurements of nutrients and related metabolites in foods, dietary supplements, and serum and plasma samples. These programs have been developed in collaboration with the National Institutes of Health to assist measurement communities in their efforts to achieve accurate results that are comparable among different laboratories and over time. Targeted analytes include micronutrients, botanical markers, nutritional elements, contaminants, fatty acids, and vitamin D metabolites.

Development and certification of green tea-containing standard reference materials.

A suite of three green tea-containing Standard Reference Materials (SRMs) has been issued by the National Institute of Standards and Technology (NIST): SRM 3254 Camellia sinensis (Green Tea) Leaves, SRM 3255 Camellia sinensis (Green Tea) Extract, and SRM 3256 Green Tea-Containing Solid Oral Dosage Form. The materials are characterized for catechins, xanthine alkaloids, theanine, and toxic elements. As many as five methods were used in assigning certified and reference values to the constituents, with measurements carried out at NIST and at collaborating laboratories. The materials are intended for use in the development and validation of new analytical methods, and for use as control materials as a component in the support of claims of metrological traceability.

Certification of vitamins and carotenoids in SRM 3280 multivitamin/multielement tablets.

A new multivitamin/multielement dietary supplement Standard Reference Material (SRM) has been issued by the National Institute of Standards and Technology (NIST), with certified and reference concentration values for 13 vitamins, 24 elements, and 2 carotenoids. The constituents have been measured by multiple analytical methods with data contributed by NIST and by collaborating laboratories. This effort included the first use of isotope dilution mass spectrometry for value assignment of both fat-soluble vitamins (FSVs) and water-soluble vitamins (WSVs). Excellent agreement was obtained among the methods, with relative expanded uncertainties for the certified concentration values typically ranging from <2% to 15% for vitamins.

Photoluminescence spectroscopy of anthrathiophenes and benzonaphthothiophenes in Shpol'skii matrixes.

The dispersion of harmful oil components into the ocean waters could pose long-term risks to flora and fauna. Due to the complexity of oil-contaminated sites, the unambiguous identification and quantitation of environmental pollutants often requires the sequence of high-performance liquid chromatography and gas chromatography-mass spectrometry. A classic example is the analysis of polycyclic aromatic hydrocarbons. This article tackles a different aspect of environmental analysis as it focuses on the Shpol'skii spectroscopy of polycyclic aromatic sulfur heterocycles, specifically those belonging to the subgroups often known as anthrathiophenes and benzonaphthothiophenes. Photoluminescence measurements were made with a commercial spectrofluorimeter equipped with a continuous wave excitation source for steady state measurements and a pulsed excitation source for time-resolved measurements in the phosphorescence time domain. To the extent of our literature search, this is the first report on the 4.2 K fluorescence and phosphorescence spectra of anthrathiophenes and benzonaphthothiophenes, and the 77 K and 4.2 K phosphorescence lifetimes of benzonaphthothiophenes. 77 K and 4.2 K analytical figures of merit revealed the possibility to detect the studied compounds at the parts-per-billion (ng mL-1) concentration levels. The spectral and lifetime data gathered in this article provides the required information to choose an appropriate photoluminescence technique for the analysis of four-ring polycyclic aromatic sulfur heterocycles in complex environmental extracts.

External Quality Assessment of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) assays.

The discovery that mutations of the CYP24A1 gene are a cause of idiopathic infantile hypercalcemia (IIH) has revived interest in measuring serum 24,25(OH)2D3. Several studies have also suggested that a high 25-hydroxyvitamin D3(25-OHD3):24,25(OH)2D3 ratio might provide additional diagnostic information in the investigation of vitamin D deficiency. Measurement of 24,25(OH)2D3 is necessarily restricted to laboratories with mass spectrometry methods although cross reactivity of the metabolite in immunoassays for 25-OHD is a potential cause of misleading results. The international External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) was set up in 1989. In 2013 DEQAS became an accuracy based EQA for 25-OHD with 'target values' assigned by the National Institute of Standards and Technology (NIST) Reference Measurement Procedure (RMP). A pilot scheme for serum 24,25(OH)2D3 was started in 2015 and participants were asked to measure the metabolite on each of the 5 samples sent out for 25-OHD. Inter-laboratory agreement was poor but this may reflect methodological differences, in particular different approaches to assay standardization. An important potential contribution to reducing variability among assays was the development by NIST of a 24,25(OH)2D3 RMP and its use in assigning values to SRMs 972a, 2973 and 2971, supported by the NIH Office of Dietary Supplements (ODS) as part of the Vitamin D Standardization Program (VDSP) effort.

Certification of standard reference materials containing bitter orange.

A suite of three dietary supplement standard reference materials (SRMs) containing bitter orange has been developed, and the levels of five alkaloids and caffeine have been measured by multiple analytical methods. Synephrine, octopamine, tyramine, N-methyltyramine, hordenine, total alkaloids, and caffeine were determined by as many as six analytical methods, with measurements performed at the National Institute of Standards and Technology and at two collaborating laboratories. The methods offer substantial independence, with two types of extractions, two separation methods, and four detection methods. Excellent agreement was obtained among the measurements, with data reproducibility for most methods and analytes better than 5% relative standard deviation. The bitter-orange-containing dietary supplement SRMs are intended primarily for use as measurement controls and for use in the development and validation of analytical methods.

Hydroxyvitamin D assays: An historical perspective from DEQAS.

Recent years have seen a substantial increase in demand for 25-hydroxyvitamin D (25-OHD) assays. DEQAS (the Vitamin D External Quality Assessment Scheme) has been monitoring the performance of these assays since 1989. The first DEQAS distribution was in June 1989 and results were submitted by 13 laboratories in the UK, two of which used HPLC/UV; the rest used ligand binding assays with a tritium tracer. Inter-laboratory CVs (ALTM) ranged from 29.3% (42.7nmol/L) to 53.7% (20.0nmol/L). Currently the scheme has participants in 56 countries using 30 methods or variants of methods. In January 2017, 918 participants returned results and inter-laboratory CVs (ALTM) ranged from 10.3% (73.1nmol/L) to 15.3% (29.4nmol/L). Over the last 27 years, there have been a number of significant milestones in assay development. The first major advance was the development of an iodinated 25-OHD tracer by Hollis and Napoli in 1992, subsequently used in an RIA kit marketed by DiaSorin. This and other commercial radioimmunoassays that followed brought 25-OHD assays within reach of many more non-specialist routine laboratories. With the introduction of fully automated non-isotopic assays without solvent extraction, measurement of 25-OHD became available to any clinical chemistry laboratory with an appropriate analytical platform. However, as the limitations of these non-extraction assays became apparent more laboratories started using LC-MS/MS methodology. Meanwhile the variable accuracy of 25-OHD methods has been addressed by the Vitamin D Standardization Program (VDSP) which encourages manufacturers to produce methods traceable to the reference measurement procedures (RMPs) of NIST, University of Ghent and the Centers for Disease Control and Prevention (CDC). DEQAS changed to an accuracy-based scheme in 2013 and now assesses assay accuracy against the NIST RMP. This review will use DEQAS results and statistics to chart the historical development in 25-OHD assay technology and highlight some of the problems encountered in obtaining reliable results for this most challenging of analytes.

Determination of HBCD, PBDEs and MeO-BDEs in California sea lions (Zalophus californianus) stranded between 1993 and 2003.

Blubber samples from male California sea lions (Zalphophus californianus) stranded between 1993 and 2003 were analyzed for 27 polybrominated diphenyl ether (PBDE) congeners, three isomers of hexabromocyclododecane (HBCD) and 14 methoxylated polybrominated diphenyl ether (MeO-BDE) congeners. Total PBDEs ranged from 450 ng/g to 4740 ng/g wet mass and total HBCD ranged from < 0.3 ng/g to 12 ng/g wet mass. The concentration of HBCD increased from 0.7 ng/g to12.0 ng/g wet mass in sea lion blubber between 1993 and 2003. However, no significant temporal trend was observed for any of the other brominated compounds over this 10 year period. Only one of the 14 MeO-BDE congeners was detected in the blubber samples, 6-methoxy-2,2',4,4'-tetrabromodiphenyl ether (6-MeO-BDE 47), and concentrations ranged from < 0.2 ng/g to 12 ng/g wet mass. A bromo-, chloro-heterocyclic compound, 1,1'-dimethyl-tetrabromo-dichloro-2,2'-bipyrrole (DBP-Br4Cl2), previously reported in marine species along the Pacific coast, was also identified in the sea lion blubber. DBP-Br4Cl2 ranged from 44 ng/g wet mass to 660 ng/g wet mass and was present at concentrations rivaling the dominant PBDE congener, BDE 47 (2,2',4,4'-tetrabromodiphenyl ether). Concentrations of DBP-Br4Cl2 were positively correlated with 6-MeO-BDE 47 (r = 0.7; p < 0.05). Both of these compounds have been identified in marine algae and sponges, and studies suggest they are both produced from natural sources. This study demonstrates that brominated compounds from both anthropogenic and biogenic sources can accumulate to similar levels in marine mammals. In addition, HBCD concentrations appear to be increasing in California sea lion populations, whereas PBDE concentrations, between 1993 and 2003, were highly variable.

Considerations in the design of an environmental specimen bank: experiences of the National Biomonitoring Specimen Bank Program.

Since 1979 the National Institute of Standards and Technology (NIST) has been involved in environmental specimen banking activities as part of the National Biomonitoring Specimen Bank (NBSB). These activities have focused on the development of procedures for the collection, processing, analysis, and long-term storage of a variety of environmental specimens including: human liver, mussels and oysters, fish tissue (liver and muscle), marine mammal tissues (blubber, liver, and kidney), and marine sediments. The experiences of the NBSB can provide valuable information to assist in the design of new specimen bank efforts. Based on the experiences of the NBSB, the issues that should be addressed in the design and operation of a valid specimen bank program are presented.

Acetaminophen prophylaxis of adverse reactions following vaccination of infants with diphtheria-pertussis-tetanus toxoids-polio vaccine.

The effect of acetaminophen on reducing the frequency and severity of adverse reactions following diphtheria-pertussis-tetanus toxoids-polio vaccine was studied in a randomized clinical trial involving 519 vaccinations in 383 infants 2 to 6 months of age and 70 infants 18 months of age. Significantly fewer local and systemic reactions were reported in acetaminophen-treated infants at 2 to 6 months of age. Acetaminophen also reduced the incidence of fever greater than 38.0 degrees C from 44% to 27%. Only 0.9% of acetaminophen-treated infants had overall behavioral changes rated as severe by parents compared to 13% of the placebo group. Infants vaccinated at 18 months of age had higher rates of systemic and local reactions than younger infants. Acetaminophen did not result in significant reductions in reaction rates after the booster at 18 months. We conclude that acetaminophen administered at the time of primary vaccination with diphtheria-pertussis-tetanus toxoids-polio can significantly reduce the frequency and severity of common adverse reactions.

Comparison of supercritical fluid extraction and Soxhlet extraction for the determination of polychlorinated biphenyls in environmental matrix standard reference materials.

Supercritical fluid extraction (SFE) was compared to traditional Soxhlet extraction for the determination of polychlorinated biphenyl congeners in three standard reference materials: SRM 1941a (Organics in Marine Sediment), SRM 1944 (New York/New Jersey Waterway Sediment) and SRM 2974 [Organics in Mussel Tissue (Mytilus edulis) (Freeze-Dried)]. The concentrations determined using SFE compared well with the certified concentrations for the majority of the polychlorinated biphenyl congeners.

Standard reference materials for chemical and biological studies of complex environmental samples.

Standard Reference Materials (SRMs) from the National Institute of Standards and Technology (NIST) are often used in methods development and interlaboratory comparison studies since they are homogeneous and readily available to the scientific community. SRM 1649 (urban dust/organics), SRM 1650 (diesel particulate matter), and SRM 1597 (complex mixture of polycyclic aromatic hydrocarbons from coal tar) are three environmental samples which have been used by the scientific community for these purposes. These SRMs were originally developed to assist laboratories in validating analytical procedures for the determination of polycyclic organic compounds in complex mixtures. In addition, these SRMs have been valuable for the comparison of methodologies for bacterial bioassays and the development of bioassay-directed fractionation and bioassay-directed chemical analysis techniques. Most recently these SRMs were chosen for use as test samples in a collaborative study coordinated by the World Health Organization--International Programme on Chemical Safety. This paper provides a summary of much of the work to date (published and unpublished) on the chemical and biological characterization of these three SRMs. Information regarding the availability of other NIST SRMs that might be useful for these types of studies are provided also.

Comparison of liquid and supercritical fluid chromatography for the separation of enantiomers on chiral stationary phases.

Comparisons of liquid (LC) and supercritical fluid chromatography (SFC) were conducted using commercially available chiral stationary phases (CSPs) bearing three different types of chiral selectors. Chiral compounds of pharmaceutical and agricultural interest were used to probe advantages of limitations of SFC relative to LC for enantiomeric separations. Column equilibrium and parameter optimization were generally accomplished more rapidly in SFC than in LC. Although improved resolution was often observed in SFC, analysis times were not always lower in SFC than in LC. In some instances, SFC provided separation capabilities not readily accessible in LC.

Development of the National Marine Mammal Tissue Bank.

The National Marine Mammal Tissue Bank (NMMTB) has been established as part of a comprehensive effort to obtain reliable information on contaminant levels in marine mammal tissues. A four component program consisting of the NMMTB, stranding networks, monitoring and quality assurance has been developed. The development and current status of the NMMTB and its relationship to the other three components will be described.

Current activities within the National Biomonitoring Specimen Bank.

The National Institute of Standards and Technology (NIST) has been involved in biological environmental specimen banking activities since 1979. These activities, which are known collectively as the National Biomonitoring Specimen Bank (NBSB), include the banking of a variety of specimens (human liver, sediment, mussels/oysters, fish tissue and marine mammal tissues) from several different projects supported by different government agencies. The two most recent projects, the Alaska Marine Mammal Tissue Archival Project (AMMTAP) and the National Marine Mammal Tissue Bank (NMMTB), focus on the collection, banking and analysis of marine mammal tissues and they are part of a comprehensive plan to address marine mammal monitoring, specimen banking and quality assurance of analytical measurements associated with contaminant analyses in marine mammals.

Biological specimen banking in Arctic research: an Alaska perspective.

The cryogenic archival of biological specimens for retrospective analysis is of significant value for present and future research on population genetics, pathology, systematics, toxicology and environmental monitoring. This realization is emphasized by the increasing support of this activity by various government agencies, institutions and international groups. The international Arctic community is no exception. Canada has been conducting such activities in association with environmental monitoring programs for many years. Similar efforts appear to be underway in other polar nations. From the perspective of the United States Arctic, the Alaska Marine Mammal Tissue Archival Project (AMMTAP) was the earliest organized effort to develop an environmental specimen bank specifically designed for longterm archival of biological specimens under cryogenic conditions. The AMMTAP emphasizes use of standardized rigorous sampling and archival protocols, procedures that minimize contamination of samples during collection and maintaining a detailed record of sample history. The development of this specimen bank, recent activities of this project and other cryogenic specimen banks being developed in Alaska are described.

Determination of PCBs and chlorinated hydrocarbons in marine mammal tissues.

Selected tissues (blubber, liver, kidney and muscle) from marine mammals, which were collected as part of the Alaska Marine Mammal Tissue Archival Project (AMMTAP), were analyzed for polychlorinated biphenyl (PCB) congeners and chlorinated pesticides. Concentrations of these compounds in the different tissues were compared and blubber was selected as the primary tissue for organic contaminant analyses for the AMMTAP based on higher levels (1-2 orders of magnitude) in this tissue compared to liver, kidney and muscle. Concentrations for 15 PCB congeners and 12 chlorinated pesticides are reported for 10 different animals of three species (northern fur seal, ringed seal and belukha whale) from five different sites.

Determination of inorganic constituents in marine mammal tissues.

Analyses of selected tissues from the Alaska Marine Mammal Tissue Archival Project (AMMTAP) have provided comprehensive information related to levels of 36 trace elements and methyl-mercury in marine mammal tissues. Liver, kidney and muscle tissues from two northern fur seals, four ringed seals and six belukha whales were analyzed. The bulk of the investigated tissues and additional tissues from a total of 65 marine mammals are banked in the AMMTAP. The results are compared to literature values for trace element concentrations in marine mammal tissues and their relevance to environmental studies is discussed.

Trace element concentrations in cetacean liver tissues archived in the National Marine Mammal Tissue Bank.

The National Biomonitoring Specimen Bank (NBSB), a collaborative project of several U.S. government agencies, includes marine mammal tissues collected for the Alaska Marine Mammal Tissue Archival Project (AMMTAP) and the National Marine Mammal Tissue Bank (NMMTB). Tissues were collected from 139 animals representing 13 species of marine mammals from around the U.S. Recently, concentrations for up to 30 elements in liver tissues of nine long-finned pilot whales (Globicephala melas), six harbor porpoises (Phocoena phocoena), and four white-sided dolphins (Lagenorhynchus acutus) from the NMMTB were measured using instrumental neutron activation analysis. Results from analyses of these tissues are presented, compared with results for liver tissues from other marine mammals from the AMMTAP, and compared with published values.