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A liquid chromatographic atmospheric-pressure ionization electrospray mass spectrometry (LC-API-ES-MS) method has been developed for the determination of five bitter orange alkaloids (synephrine, octopamine, n-methyltyramine, tyramine, and hordenine) in bitter orange-containing dietary supplement standard reference materials (SRMs). The materials represent a variety of natural, extracted, and processed sample matrices. Two extraction techniques were evaluated: pressurized-fluid extraction (PFE) and sonication extraction. The influence of different solvents, extraction temperatures, and pH were investigated for a plant material and a processed sample. The LC method uses a new approach for the separation of highly polar alkaloids. A fluorinated, silica-based stationary phase separated the five alkaloids and the internal standard terbutaline in less than 20 min. This method enabled the determination of the dominant alkaloid synephrine and other minor alkaloids in a variety of dietary supplement SRMs.

Well-characterized certified reference materials are needed by laboratories in the food testing, dietary supplement, and nutrition communities to facilitate compliance with labeling laws and improve the accuracy of information provided on product labels, so that consumers can make good choices. As a result of the enactment of the Nutrition Labeling and Education Act of 1990 and the Infant Formula Act of 1980, the National Institute of Standards and Technology (NIST) worked to develop a series of food-matrix standard reference materials (SRMs) characterized for nutrient concentrations. These include SRM 1544 Fatty Acids and Cholesterol in a Frozen Diet Composite, SRM 1546 Meat Homogenate, SRM 1548a Typical Diet, SRM 1566b Oyster Tissue, SRM 1846 Infant Formula, SRM 1946 Lake Superior Fish Tissue, SRM 1947 Lake Michigan Fish Tissue, SRM 2383 Baby Food Composite, SRM 2384 Baking Chocolate, SRM 2385 Slurried Spinach, and SRM 2387 Peanut Butter. With the enactment of the Dietary Supplement Health and Education Act of 1994, NIST has been working to develop suites of dietary supplement SRMs characterized for active and marker compounds and for toxic elements and pesticides, where appropriate. An updated SRM 1588b Organics in Cod Liver Oil, a suite of ephedra-containing materials (SRMs 3240–3245), a carrot extract in oil (SRM 3276), and a suite of ginkgo-containing materials (SRMs 3246–3248) are available. Several other materials are currently in preparation. Dietary supplements are sometimes provided in forms that are food-like; for these, values may also be assigned for nutrients, for example SRM 3244 Ephedra-Containing Protein Powder. Both the food-matrix and dietary supplement reference materials are intended primarily for validation of analytical methods. They may also be used as “primary control materials” in assignment of values to in-house (secondary) control materials to confirm accuracy and to establish measurement traceability to NIST.

The National Institute of Standards and Technology (NIST), the Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and Center for Food Safety and Applied Nutrition (CFSAN), and the National Institutes of Health (NIH), Office of Dietary Supplements (ODS) are collaborating to produce a series of standard reference materials (SRMs) for dietary supplements. Standard reference material (SRM) 3276 Carrot Extract in Oil is one in this series, with values assigned for trans-alpha-carotene, trans- and total beta-carotene, delta- and gamma-tocopherol, and twelve fatty acids. Results for carotenoids and tocopherols were obtained by use of combinations of liquid chromatography (LC), on columns of differing selectivity, with absorbance and mass spectrometric (MS) detection. Fluorescence detection also was used for the tocopherols. Results for fatty acids were obtained by use of gas chromatography (GC) with both flame-ionization and mass-spectrometric detection. This material is intended for use as a primary control material when assigning values to in-house (secondary) control materials and for validation of analytical methods for measurement of these analytes in similar matrices.

National-level health survey studies, such as the National Human Exposure Assessment Survey field program, have targeted the determination of organic contaminants in house dust in an effort to characterize human exposure in the domestic environment. As the effort to further understand human health effects in relation to organic contaminants associated with indoor dust accelerates, the need for an indoor dust Standard Reference Material (SRM) that is characterized for organic contaminants has become critical. To meet this need, a new organic contaminant house dust SRM has been developed. SRM 2585 Organic Contaminants in House Dust is intended for use in evaluating analytical methods for the determination of selected polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyl (PCB) congeners, chlorinated pesticides, and polybrominated diphenyl ether (PBDE) congeners in house dust and similar matrices. The material may also be useful for evaluation and comparison of methods or instruments used for sampling in the indoor environment. Moreover, because of the material's extensive characterization (140 organic contaminant concentrations), the material may be useful in toxicity studies related to indoor air (in vitro or in vivo). The determination of the concentrations of PAHs (including alkyl-PAHs and PAHs with molecular mass 300 and 302), PCBs, and chlorinated pesticides is reported here, and these results are compared to values reported in the literature for house dust.

For nearly three decades the National Institute of Standards and Technology (Gaithersburg, MD) has been involved in the development of Standard Reference Materials (SRMs) for the determination of organic contaminants in environmental matrices. Classes of organic contaminants characterized in these materials include polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), chlorinated pesticides, and most recently, brominated flame retardants (polybrominated diphenyl ethers [PBDEs]). Environmental matrices include fossil fuels, air and diesel particulate matter, house dust, coal tar, sediment, mussel and fish tissue, fish oil, and whale blubber. Recent SRM developments and activities have led to a number of environmental SRMs that are useful for assuring quality of analytical measurements in environmental forensics where source profiling of organic contaminants is often conducted in a range of environmental or biological matrices. Particle-related SRM developments include the issue of a ne...

Two new Standard Reference Materials (SRMs), SRM 3672 Organic Contaminants in Smokers’ Urine (Frozen) and SRM 3673 Organic Contaminants in Non-Smokers’ Urine (Frozen), have been developed in support of studies for assessment of human exposure to select organic environmental contaminants. Collaborations among three organizations resulted in certified values for 11 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and reference values for 11 phthalate metabolites, 8 environmental phenols and parabens, and 24 volatile organic compound (VOC) metabolites. Reference values are also available for creatinine and the free forms of caffeine, theobromine, ibuprofen, nicotine, cotinine, and 3-hydroxycotinine. These are the first urine Certified Reference Materials characterized for metabolites of organic environmental contaminants. Noteworthy, the mass fractions of the environmental organic contaminants in the two SRMs are within the ranges reported in population survey studies such as the National Health and Nutrition Examination Survey (NHANES) and the Canadian Health Measures Survey (CHMS). These SRMs will be useful as quality control samples for ensuring compatibility of results among population survey studies and will fill a void to assess the accuracy of analytical methods used in studies monitoring human exposure to these organic environmental contaminants.

For the past 25 years the National Institute of Standards and Technology (NIST) has developed certified reference materials (CRMs), known as standard reference materials (SRMs), for determination of organic contaminants in environmental matrices. Assignment of certified concentrations has usually been based on combining results from two or more independent analytical methods. The first-generation environmental-matrix SRMs were issued with certified concentrations for a limited number (5 to 10) of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Improvements in the analytical certification approach significantly expanded the number and classes of contaminants determined. Environmental-matrix SRMs currently available include air and diesel particulate matter, coal tar, marine and river sediment, mussel tissue, fish oil and tissue, and human serum, with concentrations typically assigned for 50 to 90 organic contaminants, for example PAHs, nitro-substituted PAHs, PCBs, chlorinated pesticides, and polybrominated diphenyl ethers (PBDEs).

The objective of the study was to assess l-5-hydroxytryptophan's (l-5HTP) augmentation effect on the neuroendocrine response to a SSRI (citalopram). A neuroendocrine challenge study was conducted in healthy Asian male subjects. The neuroendocrine response to oral citalopram and l-5HTP was measured primarily as the prolactin and cortisol area under the response curve (or AUC). The study comprised 2 studies: Study 1. A double blind, randomised dose ranging study was conducted with l-5HTP (50-200 mg) to explore the prolactin and/or cortisol dose response and select a dose that provided a threshold neuroendocrine response. Study 2. A randomized comparison of citalopram 20 vs 40 mg was used to assess the effect of these doses on prolactin and cortisol. Based on the results of the dose response assessments with l-5HTP and cortisol, 200 mg l-5HTP was subsequently used in Study 2 to explore the augmentation of the neuroendocrine response to 20 mg citalopram. Citalopram, but not l-5HTP, increased prolactin AUC(0-3h) while 5HTP and citalopram increased cortisol AUC(0-3h). A 200 mg dose of l-5HTP significantly augmented the prolactin and cortisol response AUC(0-3h) to 20mg oral citalopram. The results of the study suggest that an augmented neuroendocrine challenge may be a suitable marker to demonstrate increased 5-HT-mediated responses when exploring novel agents as improved SSRIs.

A polymer-based RP sorbent was prepared by immobilizing a poly(ethylene-co-acrylic acid) copolymer with an acid mass fraction of 5% on silica by using a 3-glycidoxypro-pyl linkage. 13 C cross-polarization/magic angle spinning NMR spectroscopy of the sorbent, either in the dry state or suspended in the mobile phase, showed an increase in mobility at elevated temperatures. Alkyl chain segments with gauche conformations were more mobile than chain segments with trans conformations. The strength of the 13 C- 1 H dipolar couplings in the alkyl chains was measured using the constant time dipolar and chemical shift pulse sequence, revealing less molecular motion for the trans conformation. Non-linear van't Hoff plots were observed for separations of shape-constrained solutes (such as geometric β-carotene isomers and polycyclic aromatic hydrocarbons). At higher temperatures, the retention behavior was similar to that of monomeric C 18 sorbents, whereas at ambient and lower temperatures, enhanced shape-selective properties were exhibited similar to those of polymeric C 30 sorbents.

Aims The aim of this study was to evaluate the effect of rifampicin co-administration on the pharmacokinetics of ruboxistaurin and its active metabolite, N-desmethyl ruboxistaurin and, in addition, to compare the changes in pharmacokinetics of ruboxistaurin and N-desmethyl ruboxistaurin with the urinary 6β-hydroxycortisol : cortisol ratio. Ruboxistaurin is a specific protein-kinase-C β inhibitor in clinical development for the treatment of diabetic microvascular complications. Methods This was a two-period, one-sequence study. Sixteen healthy male subjects completed both study periods. In period one, a single 64 mg oral dose of ruboxistaurin was administered. In period two, 600 mg rifampicin was administered daily for 9 days, during which another single 64 mg ruboxistaurin dose was administered on day 7. Blood samples were collected and assayed for ruboxistaurin and N-desmethyl ruboxistaurin. CYP3A4 induction was assessed by ratios of urinary 6β-hydroxycortisol : cortisol (6β-OHC : C) obtained via 24 h and morning-spot sampling techniques. Results Following repeated doses of rifampicin, both the mean Cmax and AUC(0,∞) of ruboxistaurin were significantly reduced by approximately 95% (P ≤ 0.001). For the metabolite, the mean Cmax decreased by 68% (P ≤ 0.001), and AUC(0,∞) decreased by 77% (P ≤ 0.001). The tmax values did not appear affected. The 6β-OHC : C ratios from both 24 h and morning spot methods increased significantly, consistent with CYP3A4 induction. Conclusions The effect of rifampicin co-administration on the exposure of ruboxistaurin is consistent with ruboxistaurin being a substrate of CYP3A4. Therefore, co-administration with known CYP3A4 inducing agents (rifampicin, carbamazepine, phenobarbital, etc.) may decrease the concentrations of ruboxistaurin and N-desmethyl-ruboxistaurin. In this study, 6β OHC : C ratios substantially underestimated the impact of rifampicin on ruboxistaurin.

Ruboxistaurin, a specific inhibitor of the beta(1) and beta(2) isoforms of protein kinase C, is currently in clinical development for the treatment of several diabetic microvascular complications. The major metabolite, N-desmethyl ruboxistaurin (metabolite 338522), is equipotent in its inhibitory activity. The elimination of ruboxistaurin and its metabolites is primarily through bile and the faecal route, with urinary excretion constituting only a minor route.To assess the effects of chronic renal insufficiency on the pharmacokinetics of ruboxistaurin and metabolite 338522.Six healthy subjects (creatinine clearance80 mL/min/1.73 m(2)) and six end-stage renal disease (ESRD) subjects requiring long-term haemodialysis were studied. All subjects received a single oral dose of ruboxistaurin 32 mg followed by serial blood sampling up to 72 hours. ESRD subjects underwent haemodialysis approximately 58 hours after dosing, with blood samples obtained immediately before and after dialysis.No differences were observed in the pharmacokinetic parameters (area under the plasma concentration-time curve from time zero to infinity [AUC(infinity)], maximum plasma concentration [C(max)] and elimination half-life [t(1/2)]) of ruboxistaurin and metabolite 338522 between healthy and ESRD subjects Plasma concentrations of ruboxistaurin were below the lower limit of quantification by the time of haemodialysis. The predicted post-dialysis plasma concentrations of metabolite 338522 were not statistically different from the observed values (p=0.163). Ruboxistaurin was well tolerated in both groups of subjects.These results indicate that the kidney is not an important route of metabolism or excretion for ruboxistaurin and metabolite 338522. Based on the pharmacokinetic and tolerability findings, no formal dosage adjustment of ruboxistaurin should be required for patients with any degree of renal impairment who are undergoing haemodialysis.

Since 1987, the Alaska Marine Mammal Tissue Archival Project (AMMTAP) has collected tissues from 18 marine mammal species. Specimens are archived in the National Institute of Standards and Technology's National Biomonitoring Specimen Bank (NIST-NBSB). AMMTAP has collected blubber, liver and/or kidney specimens from a number of ringed seals (Phoca hispida) from the areas near Nome and Barrow, Alaska and walruses (Odobenus rosmarus) from several locations in the Bering Sea. Thirty-three ringed seal and 15 walrus blubber samples from the NIST-NBSB were analyzed for persistent organic pollutants (POPs). The compounds determined included PCBs (28 congeners or congener groups), DDT and related compounds, hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs), chlordanes, dieldrin, and mirex. POP concentrations in ringed seal blubber were significantly higher in Barrow than in Nome when statistically accounting for the interaction of age and gender; HCB, however, was not statistically different between the two locations. Unlike males, POP concentrations and age were not significantly correlated in females probably as a result of lactational loss. POP concentrations in walrus blubber were lower than in ringed seal blubber for SigmaPCBs, chlordanes, and HCHs, but higher for dieldrin and mirex. POP concentrations in ringed seals and walrus from Alaska provide further evidence that the western Arctic tends to have lower or similar POP concentrations compared to the eastern Canadian Arctic.

Polybrominated diphenyl ethers (PBDEs) have been measured for the first time in three different indoor dust Standard Reference Materials (SRMs) prepared by the National Institute of Standards and Technology (NIST). Two of these, SRM 2583 (Trace Elements in Indoor Dust) and SRM 2584 (Trace Elements in Indoor Dust), have been certified previously for lead and other inorganic constituents. A third, SRM 2585 (Organics in Indoor Dust), is a new indoor dust reference material prepared by NIST which will be certified for various organic compounds (polycyclic aromatic hydrocarbons, pesticides and polychlorinated biphenyls) in 2005 including certified concentrations for 16 individual PBDE congeners and reference values for an additional three PBDE congeners. Dust SRMs were analyzed for 30 PBDE congeners using high-resolution gas chromatography combined with low-resolution mass spectrometry operated in both negative chemical ionization (GC/ECNI-MS) and electron impact ionization (GC/EI-MS) modes. Sensitivity was an order of magnitude higher using GC/ECNI-MS relative to GC/EI-MS. These SRMs have been characterized and compared to the three PBDE commercial products (pentaBDE, octaBDE and decaBDE). PentaBDE and DecaBDE were present in all three SRMs and were the dominant commercial products, making up approximately 33% and 58%, respectively. Recent studies suggest that house dust may be a leading source of human exposure to PBDEs. These SRMs are the first reference materials with certified concentrations for PBDEs, which will aid in validating future measurements of PBDEs in house dust and other similar matrices.

This open-label study investigated the effect of exenatide coadministration on the steady-state plasma pharmacokinetics of digoxin. A total of 21 healthy male subjects received digoxin (day 1, 0.5 mg twice daily; days 2-12, 0.25 mg once daily) and exenatide (days 8-12, 10 μg twice daily). Digoxin plasma and urine concentrations were measured on days 7 and 12. Exenatide coadministration did not change the overall 24-hour steady-state digoxin exposure (AUC τ , s s ) and C m i n , s s but caused a 17% decrease in mean plasma digoxin C m a s , s s (1.40 to 1.16 ng/mL) and an increuse in digoxin t m a x , s s (median increase, 2.5 hours). Although the decrease in digoxin C m a x , s s was statistically significant, peak concentrations were within the therapeutic concentration range in all subjects. Digoxin urinary pharmacokinetic parameters were not altered. Gastrointestinal symptoms, the most common adverse effects of exenatide, decreased over time. Exenatide administration does not cause any changes in digoxin steady-state pharmacokinetics that would be expected to have clinical sequelae; thus, dosage adjustment does not appear warranted, based on pharmacokinetic considerations.

Alamifovir, a purine nucleotide analogue prodrug, and its hydrolyzed derivatives have shown preclincal efficacy activity against wild-type and lamivudine-resistant hepatitis B virus. Two studies were conducted to examine the single- and multiple-dose alamifovir pharmacokinetics after oral administration in healthy males. In study 1, subjects were given single doses (0.2 to 80 mg), with a subset receiving 20 mg in a fed state. Study 2 subjects were dosed with 2.5 to 15 mg twice daily for 15 days. Plasma samples were collected over 72 h in study 1 and over 24 h on days 1 and 15 in study 2. Concentrations of alamifovir and its major metabolites were determined using liquid chromatography/tandem mass spectrometry methods. The data were analyzed using a noncompartmental technique. Although alamifovir was rapidly absorbed, there was limited systemic exposure due to its rapid hydrolysis and formation of at least three metabolites, suggesting that alamifovir acts as a prodrug. The major metabolites detected were 602074 and 602076, with 602075 detectable only in higher-dose groups. Maximum 602074 plasma concentration was achieved at approximately 0.5 h ( T max ) and declined with a 1- to 2-h terminal half-life ( t 1/2 ). Maximum concentrations of 602076 ( C max ) averaged 10% of the 602074 C max and reached T max in 2.5 h with a 4-h t 1/2 . Food appeared to decrease the extent of absorption of the compound. Multiple dosing resulted in minimal accumulation, and the concentrations following multiple doses could be predicted using the single-dose data. Alamifovir was well tolerated and the pharmacokinetics were characterized in these studies.

We examined the relationships among IGF binding protein (IGFBP)-1, insulin sensitivity, and leptin in different ethnic groups (Asian Indians, Chinese, and Caucasians) using the euglycemic hyperinsulinemic clamp. Ten healthy, young and nondiabetic subjects of each ethnic group, matched for body mass index, age, and physical activity were studied. A euglycemic clamp was performed on all subjects. IGFBP-1, insulin, and leptin were measured after fasting and during the clamp. Fasting IGFBP-1 concentration was highest in Chinese (P = 0.027). Asian Indians had the lowest insulin sensitivity index (P = 0.006). The ratio of insulin to IGFBP-1 at fasting and throughout the euglycemic clamp was higher in Asian Indians. Fasting IGFBP-1 had a strong negative correlation with fasting leptin levels (r = -0.715, P = 0.001). Multiple linear regression demonstrated that fasting insulin, leptin, ethnicity, and insulin sensitivity were significant predictors for fasting IGFBP-1. IGFBP-1 is independently determined by ethnicity, insulin sensitivity, and leptin in glucose-tolerant men. The presence of relative insulin resistance and low fasting IGFBP-1 levels in Asian Indians may contribute to their higher risk of developing diabetes and cardiovascular disease.

Background/Aims Alamifovir is a purine nucleotide analogue prodrug that shows potent activity against wild type and lamivudine resistant hepatitis B virus in preclinical studies. The aim of this study was to assess the safety and potential antiviral effects of alamifovir in humans. Methods A randomised, placebo controlled, dose escalation study of oral alamifovir was conducted in 66 chronic hepatitis B infected patients who were selected based on stable HBV DNA (>10 5 copies/ml), with no significant liver pathology. They received either placebo or alamifovir at a total daily dose ranging from 2.5 to 20mg in single or divided doses for 28 days and were followed up for approximately 12 weeks after cessation of treatment. Results All doses showed significant antiviral activity, with mean plasma viral load reductions ranging from 1.5 to 2.6 log 10 after 28 days of dosing. Once and twice daily regimen for the same daily dose (5mg BID vs 10mg QD, 10mg BID vs 20mg QD) showed no apparent difference in the rate and extent of viral decline, or viral reduction at day 28. Post-treatment viral suppression was dose dependent. There were no serious adverse events attributable to study drug, nor were significant dose related events identified. Conclusions Alamifovir has shown potent in vivo anti-HBV activity, with a favourable safety profile.

Polybrominated diphenyl ether (PBDE) congeners and components of the complex mixture toxaphene are stable in the environment and readily bioaccumulated into wildlife and human tissues. PBDEs are presently used in large quantities worldwide as flame retardants in textiles, furniture, computer equipment, and cables. Toxaphene is a complex mixture of chlorinated bornanes and bornenes that was the most heavily used pesticide in the United States until it was banned in 1982; however, some countries continue to use toxaphene. The National Institute of Standards and Technology has quantified PBDE congeners and toxaphene in several available Standard Reference Materials (SRMs) using methods of gas chromatography with electron impact mass spectrometry (GC-EI-MS) and GC negative chemical ionization (NCI) MS, respectively. SRM 1588a Organics in Cod Liver Oil and SRM 1945 Organics in Whale Blubber were examined for PBDE congeners 47, 99, 100, 153, and 154, total toxaphene, and toxaphene congeners 26, 50, and 62. SRM 1946 Lake Superior Fish Tissue was also examined for total toxaphene and toxaphene congeners. The sum of the PBDE congeners (mean, (1 SD) wet basis) for SRM 1945 was 150 ng g(-1) (7 ng g(-1)). The concentration of PBDE 47 in SRM 1588a was 82.7 ng g(-1) (2.8 ng g(-1)). Other PBDEs were detected in SRM 1588a but were not quantified due their low levels. The total toxaphene (wet mass basis) was 1,210 ng g(-1) (127 ng g(-1)), 1,960 ng g(-1) (133 ng g(-1)), and 3,980 ng g(-1) (248 ng g(-1)) in SRMs 1945, 1946, and 1588a, respectively. The values for PBDEs and toxaphene determined in the SRMs, while not certified, indicate that the SRMs will be suitable control materials for PBDE and toxaphene analyses.

Three new mussel tissue standard reference materials (SRMs) have been developed by the National Institute of Standards and Technology (NIST) for the determination of the concentrations of organic contaminants. The most recently prepared material, SRM 1974b, is a fresh frozen tissue homogenate prepared from mussels ( Mytilus edulis) collected in Boston Harbor, Massachusetts. The other two materials, SRMs 2977 and 2978, are freeze-dried tissue homogenates prepared from mussels collected in Guanabara Bay, Brazil and Raritan Bay, New Jersey, respectively. All three new mussel tissue SRMs complement the current suite of marine natural-matrix SRMs available from NIST that are characterized for a wide range of contaminants (organic and inorganic). SRM 1974b has been developed to replace its predecessor SRM 1974a, Organics in Mussel Tissue, for which the supply is depleted. Similarly, SRMs 2977 and 2978 were developed to replace a previously available (supply depleted) freeze-dried version of SRM 1974a, SRM 2974, Organics in Freeze-Dried Mussel Tissue. SRM 1974b is the third in a series of fresh frozen mussel tissue homogenate SRMs prepared from mussels collected in Boston Harbor starting in 1988. SRM 1974b has certified concentration values for 22 polycyclic aromatic hydrocarbons (PAHs), 31 polychlorinated biphenyl congeners (PCBs), and 7 chlorinated pesticides. Reference values are provided for additional constituents: 16 PAHs, 8 PCBs plus total PCBs, 6 pesticides, total extractable organics, methylmercury, and 11 trace elements. PAH concentrations range from about 2 ng g(-1 )dry mass (cyclopenta[ cd]pyrene) to 180 ng g(-1 )dry mass (pyrene). PCB concentrations range from about 2 ng g(-1 )dry mass (PCB 157) to 120 ng g(-1 )dry mass (PCB 153). The reference value for total PCBs in SRM 1974b is (2020 +/- 420) ng g(-1 )dry mass. Pesticide concentrations range from about 4 ng g(-1 )dry mass (4,4'-DDT) to 40 ng g(-1 )dry mass (4,4'-DDE). SRM 2977 has certified values for 14 PAHs, 25 PCB congeners, 7 pesticides, 6 trace elements, and methylmercury. Reference values for 16 additional PAHs and 9 inorganic constituents are provided, and information values are given for 23 additional trace elements. SRM 2978 has certified and reference concentrations for 41 and 22 organic compounds, respectively, and contains contaminant levels similar to those of SRM 1974b. Organic contaminant levels in SRM 2977 (mussels from Guanabara Bay, Brazil) are typically a factor of 2 to 4 lower than those in SRM 1974b and SRM 2978. The organic contaminant concentrations in each new mussel tissue SRM are presented and compared in this paper. In addition, a chronological review of contaminant concentrations associated with mussels collected in Boston Harbor is discussed as well as a stability assessment of SRM 1974a.

Two new marine sediment standard reference materials (SRMs), SRM 1941b Organics in Marine Sediment and SRM 1944 New York/New Jersey Waterway Sediment, have been recently issued by the National Institute of Standards and Technology (NIST) for the determination of organic contaminants including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyl (PCB) congeners, and chlorinated pesticides. Both sediment SRMs were analyzed using multiple analytical methods including gas chromatography/mass spectrometry (GC/MS) on columns with different selectivity, reversed-phase liquid chromatography with fluorescence detection (for PAHs only), and GC with electron capture detection (for PCBs and pesticides only). SRM 1941b has certified concentrations for 24 PAHs, 29 PCB congeners, and 7 pesticides, and SRM 1944 has certified concentrations for 24 PAHs, 29 PCB congeners, and 4 pesticides. Reference concentrations are also provided for an additional 58 (SRM 1941b) and 39 (SRM 1944) PAHs, PCB congeners, and pesticides. SRM 1944, which was collected from multiple sites within New York/New Jersey coastal waterways, has contaminant concentrations that are generally a factor of 10-20 greater than SRM 1941b, which was collected in the Baltimore (Maryland) harbor. These two SRMs represent the most extensively characterized marine sediment certified reference materials available for the determination of organic contaminants.

The results of Global Positioning System (GPS) mapping and Geographic Information System (GIS) analysis of Civil War earthworks in Beaufort and Jasper counties, South Carolina, are presented. Most earthworks were part of a defensive system built by Confederate forces over the course of the war to protect the Charleston to Savannah railroad, which itself was part of a vital supply line allowing rapid transport of men and materiel throughout the Confederacy. For most of the war, Union forces were deployed at Port Royal Sound less than 40 km from the railroad. The Confederates met this threat through fixed defenses at strategic locations combined with rapid movement of troops by rail. This strategy and these tactics are understandable within the geographic context provided by GPS/GIS technology and a military context provided by a detailed campaign history.

A series of bonded phases were synthesized from consecutive length alkylsilanes ranging from C13 through C18, with three different bonding chemistries (monomeric, solution polymerized, and surface polymerized) at each phase length. The phases were characterized in terms of methylene selectivity, shape selectivity, and band broadening. No significant chromatographic differences were found to result from the synthetic routes, except that the different bonding chemistries provide a different range of bonding densities. For bonding densities ranging from 2 to 8 μmol/m2, a linear increase in methylene selectivity was observed with increasing bonding density. Over the narrow range of bonded phase lengths investigated, shape selectivity is more dependent on density than phase length.

Aim To compare the pharmacokinetic profiles and dose proportionality of olanzapine in Chinese and Caucasian subjects. Methods Randomized, three-period study with 12 Chinese and 12 Caucasian, healthy, male subjects administered 2.5, 5 and 10 mg olanzapine. Noncompartmental pharmacokinetic parameters were derived. Results No statistically significant racial differences in the weight-normalized pharmacokinetic parameters were observed except for Vz/Fnorm, which was 17% lower at the 5- and 10-mg dose in the Chinese group (95% confidence interval 8.49, 10.1 and 8.05, 9.73, respectively), compared with the Caucasian group (9.53, 12.8 and 9.39, 12.0, respectively). Olanzapine's pharmacokinetics were linear and dose proportional in both racial groups. Conclusion The pharmacokinetics of olanzapine are similar in both Chinese and Caucasian racial groups.

On December 14, 1997, 62 rough-toothed dolphins (Steno bredanensis) stranded on Cape San Blas, on the Florida coast of the Gulf of Mexico. Approximately 30 animals died either on the beach or in rehabilitation facilities. Two were successfully rehabilitated and released. Liver, kidney, blubber, and muscle tissues were collected from 15 animals that died on the beach. Portions of the liver and kidney from each dolphin were analyzed using instrumental neutron activation analysis and inductively coupled plasma mass spectrometry to determine mass fractions of 37 elements. Levels of several electrolytes (Na, Cl, K, Br, Rb, I, Cs) and of the essential trace elements Fe, Cu, and Zn in both tissues were similar to those found in other Odontoceti. Mass fractions of Ca ranged from 60 mg/kg to 1,200 mg/kg (wet mass basis), indicating significant inhomogeneity in the kidney tissues of several animals. Necropsy reports noted that the kidneys of many of these animals contained fibrous nodules. The measured Ca inhomogeneity may be due to mineralization of the fibrous kidney tissue. Hepatic levels of Hg and Se were at the high end of the ranges generally found in livers of other Odontoceti and were slightly higher in animals with fibrous kidneys than in the others. Mass fractions of Se, Ag, and Hg in liver tissues increased with the size and age of the animals indicating accumulation of these elements in the liver with age. Results also indicate that Se and Hg accumulate in rough-toothed dolphin kidney. Accumulation of these elements with age has been reported commonly for marine mammals and other species.

Background and Objectives Duloxetine, a potent dual reuptake inhibitor of serotonin and norepinephrine currently undergoing clinical investigation for treatment of depression and stress urinary incontinence, has the potential to act as both a substrate and an inhibitor of cytochrome P4502D6 (CYP2D6). Our objectives were to determine the effect of duloxetine on the pharmacokinetics of desipramine, a tricyclic antidepressant metabolized by CYP2D6 (study 1), and the effect of paroxetine, a potent CYP2D6 inhibitor, on duloxetine pharmacokinetics (study 2). Methods Subjects were healthy men and women between 21 and 63 years old. All subjects were genotypically CYP2D6 extensive metabolizers. In study 1, 50 mg of desipramine was administered as a single dose alone and in the presence of steady-state duloxetine 60 mg twice daily. In study 2, steady-state pharmacokinetics of duloxetine 40 mg once daily were determined in the presence and absence of steady-state paroxetine 20 mg once daily. Results Duloxetine increased the maximum plasma concentration of desipramine 1.7-fold and the area under the concentration-time curve 2.9-fold. Paroxetine increased the maximum plasma concentration of duloxetine and the area under the concentration-time curve at steady state 1.6-fold. Reports of adverse events were similar whether duloxetine was administered alone or in combination with desipramine or paroxetine. Conclusion Duloxetine 60 mg twice daily is a moderately potent CYP2D6 inhibitor, intermediate between paroxetine and sertraline. The potent CYP2D6 inhibitor paroxetine has a moderate effect on duloxetine concentrations. The results of these 2 studies suggest that caution should be used when CYP2D6 substrates and inhibitors are coadministered with duloxetine. Clinical Pharmacology & Therapeutics (2003) 73, 170–177; doi: 10.1067/mcp.2003.28

A new Standard Reference Material (SRM) for use in characterizing general aspects of liquid chromatographic column performance is described. SRM 870 Column Performance Test Mixture for Liquid Chromatography contains five components: uracil, toluene, ethylbenzene, quinizarin, and amitriptyline, and is intended to provide indications of column void volume, hydrophobicity, methylene selectivity, activity toward organic bases, and activity toward metal chelators. The test is performed under neutral, buffered conditions. The measurement of retention and peak asymmetry factors for the components facilitates column classification. It is anticipated that this material will be useful (1) in column selection during method development, (2) as a control material to monitor column performance over time, and (3) in quality control in column manufacturing.

The National Institute of Standards and Technology has issued numerous environmental matrix standard reference materials (SRMs) for the measurement of polycyclic aromatic hydrocarbons; however, only one SRM (diesel particulate material) was issued with certified and reference values for four nitrated-polycyclic aromatic hydrocarbons (nitro-PAH). The objective of this study was to develop an improved analytical procedure to quantify 28 mononitro- and dinitro-PAHs, including numerous isomers, in air and diesel particulate SRMs. Two air particulate matrix SRMs, SRM 1649a Urban Dust and SRM 1648 Urban Particulate Matter, and fine particulate matter, collected from Baltimore MD for use as an "interim reference material" for the determination of organic contaminants, have been characterized for nitro-PAHs. Concentrations of nitro-PAHs in all three air particulate materials were at the ng/g level with the highest nitro-PAH concentration being 2-nitrofluoranthene (range between 246 and 340 ng/g). For the three diesel particulate-related SRMs, SRM 1650a Diesel Particulate Matter, SRM 1975 Diesel Particulate Extract, and SRM 2975 Diesel Particulate Matter (Industrial Fortlift), concentrations of nitro-PAHs were in the microg/g range, with 1-nitropyrene as the dominant nitro-PAH (range between 18 and 40 microg/g). Distinct nitro-PAH isomer patterns were present between the air and diesel particulate materials. These results will provide isomer identification and reference concentrations for a large number of nitro-PAHs in the existing diesel and air particulate SRMs. Published by Elsevier Science Ltd.

Since the establishment of the Marine Corps Recruit Depot, Parris Island, the command has been dealing with an archaeological site that dates from 1562 that contains the remains of Spanish and French colonial settlements. Known as the Santa Elena/Charlesfort site, the area has been under excavation since the early 1920s. Because of its importance to the colonial history of the United States, the site has been designated a national landmark. Besides its cultural importance, the site has also served as a learning tool for the Depot in its care and handling of cultural resources. © 2003 Wiley Periodicals Inc.

The concentrations of a wide range of polychlorinated biphenyl congeners (PCBs) and chlorinated pesticides in a fish tissue Standard Reference Material (SRM) have been determined using multiple methods of analysis. This material, SRM 1946, Lake Superior Fish Tissue, was recently issued by the National Institute of Standards and Technology (NIST) and complements a suite of marine environmental natural-matrix SRMs that are currently available from NIST for the determination of organic contaminants such as aliphatic hydrocarbons, polycyclic aromatic hydrocarbons (PAHs), PCBs, and chlorinated pesticides. SRM 1946 is a fresh tissue homogenate (frozen) prepared from filleted adult lake trout (Salvelinus namaycush namaycush) collected from the Apostle Islands region of Lake Superior. SRM 1946 has certified and reference concentrations for PCB congeners, including the three non- ortho PCB congeners, and chlorinated pesticides. Certified concentrations are available for 30 PCB congeners and 15 chlorinated pesticides. Reference concentrations are available for 12 PCB congeners and 2 chlorinated pesticides. In addition, SRM 1946 is characterized for additional chemical constituents and properties: fatty acids, extractable fat, methylmercury, total mercury, selected trace elements, proximates, and caloric content. The characterization of chlorinated compounds is described in this paper with an emphasis on the approach used for the certification of the concentrations of PCB congeners and chlorinated pesticides. The PCB congener and chlorinated pesticide data are also compared to concentrations in other marine natural-matrix reference materials available from NIST (fish oil, mussel tissue, whale blubber, and a second fresh frozen fish tissue homogenate prepared from filleted adult lake trout collected from Lake Michigan) and from other organizations such as the National Research Council Canada (ground whole carp), the International Atomic Energy Agency (fish homogenate), and the European Commission Joint Research Centre [fish oils (cod and mackerel) and mussel tissue].

The National Institute of Standards and Technology (NIST) has recently issued three Standard Reference Materials (SRMs) related to diesel particulate matter: SRM 1650a, Diesel Particulate Matter; S...

The concentrations of methyl-substituted polycyclic aromatic hydrocarbons (PAHs) in three diesel particulate-related Standard Reference Materials (SRMs) have been determined using multiple methods of analysis. These three SRMs--SRM 1650a, Diesel Particulate Matter; SRM 2975, Diesel Particulate Matter (Industrial Forklift); and SRM 1975, Diesel Particulate Extract--were recently issued by the National Institute of Standards and Technology. Each material has certified and reference concentrations for PAHs including many methyl-substituted compounds. Reference concentrations are available for 21 compounds in SRM 1650a, 20 compounds in SRM 2975, and 20 compounds in SRM 1975. The characterization of the methyl-substituted PAHs is described in this article in conjunction with a description of the relative distribution of the methyl-substituted PAHs in each material.

Aims To test the hypothesis that the renal clearance of moxonidine decreases when dosed with quinidine. Methods A randomized, two-period study was conducted with six healthy, male subjects orally dosed with either 0.2 mg moxonidine alone or 1 h after 400 mg quinidine sulphate. Pharmacokinetic parameters were calculated using a noncompartmental analysis method. Results When coadministered, quinidine significantly increased moxonidine AUC and t1/2 by 11% and 15%, respectively, and decreased CL/F by 10% compared with the control dosing. CLR and Aeur were not significantly different. Clinically, both treatments were well tolerated. Conclusions Quinidine does not affect the renal clearance of moxonidine. The decrease in apparent total clearance of moxonidine with quinidine coadministration was possibly due to metabolic inhibition, though not likely to be clinically significant.

Because of increased interest in the marine and atmospheric sciences in elemental carbon (EC), or black carbon (BC) or soot carbon (SC), and because of the difficulties in analyzing or even defining this pervasive component of particulate carbon, it has become quite important to have appropriate reference materials for intercomparison and quality control. The NIST "urban dust" Standard Reference Material(®) SRM 1649a is useful in this respect, in part because it comprises a considerable array of inorganic and organic species, and because it exhibits a large degree of ((14)C) isotopic heterogeneity, with biomass carbon source contributions ranging from about 2 % (essentially fossil aliphatic fraction) to about 32 % (polar fraction). A primary purpose of this report is to provide documentation for the new isotopic and chemical particulate carbon data for the most recent (31 Jan. 2001) SRM 1649a Certificate of Analysis. Supporting this is a critical review of underlying international intercomparison data and methodologies, provided by 18 teams of analytical experts from 11 institutions. Key results of the intercomparison are: (1) a new, Certified Value for total carbon (TC) in SRM 1649a; (2) (14)C Reference Values for total carbon and a number of organic species, including for the first time 8 individual PAHs; and (3) elemental carbon (EC) Information Values derived from 13 analytical methods applied to this component. Results for elemental carbon, which comprised a special focus of the intercomparison, were quite diverse, reflecting the confounding of methodological-matrix artifacts, and methods that tended to probe more or less refractory regions of this universal, but ill-defined product of incomplete combustion. Availability of both chemical and (14)C speciation data for SRM 1649a holds great promise for improved analytical insight through comparative analysis (e.g., fossil/biomass partition in EC compared to PAH), and through application of the principle of isotopic mass balance.

To determine the relative inputs of polycyclic aromatic hydrocarbons (PAHs) and black carbon (BC) in environmental samples from the combustion of fossil fuels and biomass, we have developed two independent analytical methods for determining the 14C abundance of PAHs and BC. The 5730 yr half-life of 14C makes it an ideal tracer for identifying combustion products derived from fossil fuels (14C-free) versus those stemming from modern biomass (contemporary 14C). The 14C abundance of PAHs in several environmental Standard Reference Materials was measured by accelerator mass spectrometry after extraction and then purification by high-performance liquid chromatography and preparative capillary gas chromatography. This method yields pure compounds that allow for a high degree of confidence in the 14C results. The PAHs data were then used to compare and evaluate results from an operationally defined thermal oxidation method used to isolate a BC fraction. The 14C compositions of PAHs and BC were very similar and suggest that the thermal oxidation method employed for isolating BC is robust and free from interferences by non-BC components. In addition, these data indicate that both the PAHs and the BC species derive mostly from fossil fuels and/or their combustion products.

In 1981 the National Bureau of Standards, now the National Institute of Standards and Technology (NIST), issued the first natural matrix Standard Reference Material (SRM) for the determination of polycyclic aromatic compounds (PACs), SRM 1580 Organics in Shale Oil. In the next 10 years, additional natural matrix SRMs were developed including air and diesel particulate matter, petroleum crude oil, coal tar, sediment, and mussel tissue. The SRMs represented the "first generation" of natural matrix SRMs for the determination of PACs. The SRMs had "certified" values for only 5 to 12 PACs; however, their development established the foundation for the implementation of the "two or more independent analytical techniques" approach for certification of individual PACs in environmental matrices. The requirement for use of different analytical techniques spurred the development of both gas chromatography (GC) and liquid chromatography (LC) approaches for the determination of PACs. Since the mid-1990s, the "second ge...

The stability of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and chlorinated pesticides in frozen mussel tissue Standard Reference Materials (SRMs) stored at −80 °C was assessed by analyzing samples of SRM 1974, SRM 1974a, and SRM 1974b Organics in Mussel Tissue (Mytilus edulis) periodically over 25 y, 20 y, and 12 y, respectively. The most recent analyses were performed during the certification of the fourth release of this material, SRM 1974c. Results indicate the concentrations of these persistent organic pollutants have not changed during storage at −80 °C. In addition, brominated diphenyl ethers (BDEs) were quantified in each of the materials during this study. The stability information is important for on-going monitoring studies collecting large quantities of samples for future analyses (i.e., formally established specimen banking programs). Since all four mussel tissue SRMs were prepared from mussels collected at the same site in Dorchester Bay, MA, USA, the results provide a temporal trend study for these contaminants over a 17 year period (1987 to 2004).

OBJECTIVES A modified insulin tolerance test (ITT) can be used to simulate a physiological stress state through the induction of controlled hypoglycemia in healthy volunteers. This allows for evaluation of hypothalamic-pituitary-adrenocortical axis response to stress via a surge in cortical release. However, a consequence of severe, prolonged hypoglycemia is QT interval prolongation. The aim of this analysis was to confirm that blood glucose lowering to 60 mg/dL (previously identified as adequate for inducing stress) has low risk of inducing clinically significant QT prolongation. MATERIALS AND METHODS Continuous ECG monitoring was conducted as a planned sub study of an open-label, 2-period study involving 18 healthy male subjects. The QTcF response to hypoglycemia was measured over 2 identical periods, ~ 7 days apart. RESULTS An indirect- response model adequately described the pharmacological relationship between blood glucose and QTcF intervals over the time-course of the ITT. The model correctly identified the steep glucose-QT relationship as an on-off response with a large Hill coefficient of 59 and the threshold glucose, EC50, as ~ 57 mg/dL with narrow between-subject variability of 10%. Simulated QTcF profiles over the course of an ITT did not demonstrate any QTcF interval changes of clinical concern, defined as QTcF observation > 500 ms, if hypoglycemia did not reach below 60 mg/dL. The statistical prediction that the chance of a mean QTcF observation > 500 ms was < 0.0001. CONCLUSIONS Results support that an ITT maintained at or above 60 mg/dL is unlikely to cause QT prolongation in healthy volunteers and does not warrant continuous ECG monitoring in this group of subjects.

Relationships between column temperature and retention behavior are reviewed for separations in reversed-phase liquid chromatography on hydrocarbonaceous bonded phases. Changes in selectivity are observed to occur with changes in temperature for a wide variety of stationary phase types. The largest temperature effects are observed for long alkyl chain length stationary phases and liquid crystalline stationary phases. Changes in stationary phase conformational structure are characterized by spectroscopic approaches, and correlations are made with retention behavior. In general, improved separations of isomers are usually possible at reduced column temperature. Applications are presented for classes of compounds that exhibit well-defined (constrained) molecular structure.

The stability of polycyclic aromatic hydrocarbons (PAHs) in frozen mussel tissue (stored at -80 °C and -120 °C was assessed by analyzing samples of SRM 1974 and SRM 1974a, Organics in Mussel Tissue (Mytilus edulis), since the initial certification analyses. Results of analyses of SRM 1974 and SRM 1974a after 10 years and 6 years of storage, respectively, indicate that the PAH concentrations have not changed. Comparison of results from the analyses of frozen versus freeze-dried mussel tissue samples indicate significant losses of the more volatile PAH such as naphthalene and methylnaphthalenes during the freeze-drying process.

The National Institute of Standards and Technology (NIST) has recently issued several new environmental matrix SRMs, including air and diesel particulate matter, marine sediment, and mussel tissue with certified and reference concentrations for polycyclic aromatic hydrocarbons (PAHs). New marine-related SRMs include: SRM 1944 New York/New Jersey Waterway Sediment, SRM 2974 Organics in Freeze-dried Mussel Tissue, SRM 2977 Mussel Tissue (Organic Contaminants and Trace Elements), and SRM 2978 Mussel Tissue (Organic Contaminants — Raritan Bay, New Jersey). SRM 2975 Diesel Particulate Matter (Industrial Forklift) and SRM 1975 Diesel Particulate Extract (a dichloromethane extract of the particulate matter used for SRM 2975) represent two new diesel particulate-related materials. In addition two existing materials, SRM 1649a Urban Dust and SRM 1650a Diesel Particulate Matter were recently reissued with certified and reference values for over 40 PAHs.

Due to the limited number of environmental matrix certified reference materials (CRMs) with assigned values for natural levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), an interlaboratory study was undertaken by the National Institute of Standards and Technology (NIST) and Environment Canada to establish reference concentration values for selected PCDD/Fs in two well-characterized NIST Standard Reference Materials (SRMs): SRM 1649a (Urban Dust) and SRM 1944 (New York/New Jersey Waterway Sediment). Results from 14 laboratories were used to provide reference values for the seventeen 2, 3, 7, 8-substituted PCDD/F congeners, the totals for individual tetra- through hepta-substituted PCDD/F homologues, and the total amount of tetra- through hepta-substituted PCDD/Fs. The mass fractions for the individual 2, 3, 7, 8-substituted congeners range from approximately 0.01 microg/kg to 7 microg/kg dry mass.

Three types of combustion sample extracts, smokeless coal, smoky coal, and wood, were analyzed for a range of polycyclic aromatic hydrocarbons (PAHs) and polycyclic aromatic sulfur heterocycles (PASH). Standard Reference Material (SRM) 1597, Complex Mixture of PAHs from Coal Tar, was also analyzed as a control sample and for the determination of a larger number of PAHs relative to those determined previously. Target analytes included many alkyl-substituted PAHs such as dimethylphenanthrenes, methylfluoranthenes, and methylpyrenes. The analytical methods included sample clean-up and the selection of specific stationary phases to accomplish unique separations of PAHs. Clean-up involved the use of normal-phase liquid chromatographic isolation of PAHs based on the number of aromatic carbons and a total PAH fraction, PAHs in the resulting fractions were separated by gas chromatography using two stationary phases with different selectivities and analyzed using mass spectrometry. These methods are discu...

C30 self-assembled monolayers (SAMs) have been prepared on zirconia, titania, and two different silica gels by reacting C30 trichlorosilane with the humidified surfaces. 13C solid-state NMR spectroscopy indicated higher alkyl chain order on titania and zirconia materials than on the silica C30 phases. Order is inferred from the relative intensity of the main methylene carbon resonance assigned to an all-trans conformation. Carbon longitudinal relaxation time (T1C) data reveal that these ordered alkyl chains still have large-amplitude motions on submicrosecond time scales at ambient temperature. Since fast diffusional rotation about the chain axis is compatible with an all-trans conformation, T1C, carbon chemical shift, and proton line width data for the alkane rotator phase (C19) and the C30 phases were compared. Proton spin diffusion experiments were also conducted using an initial polarization gradient based on mobility differences. These experiments indicated both a higher mobility for the free end of ...

The National Institute of Standards and Technology (NIST) recently issued SRM 1649a, Urban Dust, with certified and reference values for 44 polycyclic aromatic hydrocarbons (PAHs). This material is a recertification of SRM 1649 which was issued in 1982 with certified values for only five PAHs. The PAHs were determined using the following analytical techniques: (1) reversed-phase liquid chromatography with fluorescence detection (LC-FL) for analysis of the total PAH fraction, (2) reversed-phase LC-FL for analysis of isomeric PAH fractions isolated by normal-phase LC (i.e., multidimensional LC), and (3) gas chromatography/mass spectrometry (GC/MS) for analysis of the PAH fraction using three different stationary phases, each with different selectivity for PAH separations. The results from the different techniques are compared and discussed. SRM 1649a is currently the most extensively characterized environmental matrix SRM with respect to PAH constituents.

Standard Reference Materials (SRMs) are Certified Reference Materials issued by the National Institute of Standards and Technology (NIST). Three of these materials, SRMs 1975 (Diesel Particulate Extract), 2975 (Diesel Particulate Matter, Industrial Forklift), and 1650 (Diesel Particulate Matter) are diesel particulate-related materials that are well characterized for PAH isomer distributions. SRM 1975 is a methylene chloride extract of industrial forklift diesel particulate matter and it was developed originally in response to the needs of the bioassay community for a natural environmental extract. Thirty-nine PAHs (or combinations of PAHs) were determined in SRM 1975 using various combinations of four different methods of analysis. SRM 1975 will be issued with certified concentrations for eight PAHs. In addition, reference concentrations will be provided for additional PAHs, including many alkyl substituted isomers such as methylphenanthrenes, methylpyrenes, and methylfluoranthenes. Reference va...

In reversed-phase liquid chromatography (RPLC), the separation of compound mixtures of similar polarity can present a significant challenge for the analyst. Examples of such compounds include geometric isomers present in environmental samples (e.g., polycyclic aromatic hydrocarbons, polycyclic aromatic sulfur heterocycles, and polychlorinated biphenyl congeners) and compounds of biological significance (e.g., carotenoids and steroids). In general, compounds with rigid, well-defined molecular shape are best separated using a column with enhanced shape selectivity characteristics. This perspective presents an overview of column properties that influence shape selectivity for constrained solutes. Approaches to the characterization of stationary-phase structure are described, and the findings are correlated with chromatographic performance. Finally, retention models of shape discrimination are presented that are consistent with observed retention behavior. An appreciation for shape recognition effects in RPLC will facilitate method development for certain classes of difficult to resolve compounds.

Retention indices for 80 polycyclic aromatic sulfur heterocyclic compounds (PASHs) were determined by using high-resolution capillary gas chromatography (GC) with three different stationary phases: a 5% (mole fraction) phenyl-substituted methylpolysiloxane column, a 50% (mole fraction) phenyl-substituted methylpolysiloxane column and a smectic liquid crystalline column. Retention data were obtained for the following PASHs: dibenzothiophene, 28 alkyldibenzothiophenes, naphtho[1,2- b ]thiophene, seven of the eight possible methylnaphtho[1,2- b ]thiophenes, naphtho[2,1- b ]thiophene, all eight methylnaphtho[2,1- b ]thiophenes, naphtho[2,3- b ]thiophene, the three benzo[ b ]naphthothiophene isomers (benzo[ b ]naphtho[1,2- d ]thiophene, benzo[ b ]naphtho[2,1- d ]thiophene and benzo[ b ]naphtho[2,3- d ]thiophene), and all 30 possible methylbenzo[ b ]naphthothiophene isomers. Molecular descriptors [length, breadth, thickness ( T ), and length-to-breadth ratio ( L / B )] were calculated for all the compounds studied. Correlations for retention on the liquid crystalline phase and solute geometry ( L / B and T ) ratios were investigated, and the retention was found to be highly correlated with L / B resulting in correlation coefficients ranging from r =0.68 to r =0.98.

The relationship between alkyl phase structure and chromatographic performance is investigated for a series of docosyl (C22)-modified silica surfaces. The results of solid-state nuclear magnetic resonance (NMR) spectroscopy and fluorescence spectroscopy are evaluated and correlated with liquid chromatographic retention for relevant shape-selective separations. A set of four different stationary phases was prepared by solution and surface polymerization approaches, yielding materials with surface coverages ranging from 3.6 to 7.0 μmol/m2. 13C cross polarization magic angle spinning (CP/MAS) NMR spectra indicate that a predominance of trans conformations exists for high-coverage C22 phases (>4.0 μmol/m2). Two-dimensional solid-state NMR spectroscopy (wide line separation, WISE) was utilized to evaluate the mobility of the trans and gauche alkyl chain conformations. Temperature-dependent 13C CP/MAS NMR measurements of the bonded phases exhibit large differences in the dynamic behavior of the immobilized C22 ...

The preparation of the recently released Standard Reference Material (SRM) 2383 Baby Food Composite and the process used for value assignment of nutrient concentrations are reported. SRM 2383 can be used as a control material when assigning values to in-house control materials and when validating analytical methods for measuring proximates, vitamins, and minerals in baby food and similar matrixes. The SRM was prepared as a commercial baby food would be prepared, with the same ingredients. The Certificate of Analysis for SRM 2383 provides assigned values for concentrations of proximates, vitamins, and minerals for which product labeling is required by the Nutrition Labeling and Education Act of 1990. These assigned values were based on measurements by the National Institute of Standards and Technology (NIST) and/or collaborating laboratories. Assignment of analyte concentrations based solely on analyses by collaborating laboratories is described in this paper. Certified values are provided for retinol, tocopherols, and several carotenoids including total β-carotene; the certification of and methodology used for measurement of these analytes is discussed in a companion paper (this issue, page 288). Reference values are provided for solids, ash, fat, nitrogen, protein, carbohydrate, calories, vitamin B1, vitamin B2, vitamin B6, niacin, biotin, calcium, phosphorus, magnesium, manganese, iron, zinc, copper, sodium, potassium, and chloride. Reference values for additional carotenoids are reported in the companion paper (this issue, page 288). Information values are provided for iodine, selenium, molybdenum, vitamin D, vitamin B12, folic acid, pantothenic acid, choline, inositol, sugars, total dietary fiber, and 3 classes of fats.

A previously issued National Institute of Standards and Technology (NIST) Standard Reference Material (SRM), SRM 1649, Urban Dust/Organics has been analyzed for chlorinated organic contaminants (polychlorinated biphenyls and chlorinated pesticides) to provide certified values for a new class of compounds relative to the former certification. The material will be reissued as SRM 1649a. Four different analytical techniques were used. Specifically, two different methods of extraction (Soxhlet and pressurized fluid extraction) were used in conjunction with sample analysis by gas chromatography with two different columns (5% phenyl-methyl polysiloxane and 50% methyl C-18 dimethyl polysiloxane) that exhibit distinct selectivity, and with two different modes of detection (electron capture detection and mass spectrometry). The results from these techniques were combined to generate certified concentrations for 35 PCB congeners (some in combination) and 8 chlorinated pesticides. Ancillary assessments of additional chemical and physical properties of SRM 1649a include homogeneity, moisture, total organic carbon, extractable mass, and the particle-size distribution. The approach and the results for the certification of the PCB congeners and chlorinated pesticides in SRM 1649a, and the determination of the additional chemical and physical properties are described. In addition, the determination of PCBs and chlorinated pesticides in SRM 1648, Urban Particulate Matter (a particulate material certified for inorganic constituents), is also discussed although certified values are not presented.