Increased interest in volatile organic compound (VOC) exposure has led to an increased need for consistent, systematic, and informative naming of VOC metabolites. As analytical methods have expanded to include many metabolites in a single assay, the number of acronyms in use for a single metabolite has expanded in an unplanned and inconsistent manner due to a lack of guidance or group consensus. Even though the measurement of VOC metabolites is a well-established means to investigate exposure to VOCs, a formal attempt to harmonize acronyms amongst investigators has not been published. The aim of this work is to establish a system of acronym naming that provides consistency in current acronym usage and a foundation for creating acronyms for future VOC metabolites.

Objectives Matrix differences among serum samples from non-pregnant and pregnant patients could bias measurements. Standard Reference Material 1949, Frozen Human Prenatal Serum, was developed to provide a quality assurance material for the measurement of hormones and nutritional elements throughout pregnancy. Methods Serum from non-pregnant women and women in each trimester were bottled into four levels based on pregnancy status and trimester. Liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were developed and applied to the measurement of thyroid hormones, vitamin D metabolites, and vitamin D-binding protein (VDBP). Copper, selenium, and zinc measurements were conducted by inductively coupled plasma dynamic reaction cell MS. Thyroid stimulating hormone (TSH), thyroglobulin (Tg), and thyroglobulin antibody concentrations were analyzed using immunoassays and LC-MS/MS (Tg only). Results Certified values for thyroxine and triiodothyronine, reference values for vitamin D metabolites, VDBP, selenium, copper, and zinc, and information values for reverse triiodothyronine, TSH, Tg, and Tg antibodies were assigned. Significant differences in serum concentrations were evident for all analytes across the four levels (p≤0.003). TSH measurements were significantly different (p<0.0001) among research-only immunoassays. Tg concentrations were elevated in research-only immunoassays vs. Federal Drug Administration-approved automated immunoassay and LC-MS/MS. Presence of Tg antibodies increased differences between automated immunoassay and LC-MS/MS. Conclusions The analyte concentrations' changes consistent with the literature and the demonstration of matrix interferences in immunoassay Tg measurements indicate the functionality of this material by providing a relevant matrix-matched reference material for the different stages of pregnancy.

Benzene is a known genotoxic carcinogen linked to many hematological abnormalities. S-phenylmercapturic acid (PHMA, N-Acetyl-S-(phenyl)-L-cysteine, CAS# 4775-80-8) is a urinary metabolite of benzene and is used as a biomarker to assess benzene exposure. Pre-S-phenylmercapturic acid (pre-PHMA) is a PHMA precursor that dehydrates to PHMA at acidic pH. Published analytical methods that measure urinary PHMA adjust urine samples to a wide range of pH values using several types of acid, potentially leading to highly variable results depending on the concentration of pre-PHMA in a sample. Information is lacking on the variation in sample preparation among laboratories regularly measuring PHMA and the effect of those differences on PHMA quantitation in human urine samples. To investigate the differences in PHMA quantitation, we conducted an inter-laboratory comparison that included the analysis of 50 anonymous human urine samples (25 self-identified smokers, 25 self-identified non-smokers), quality control samples, and commercially available reference samples in five laboratories using different analytical methods to determine which sample preparation methods are currently in use and compare PHMA results. Observed urinary PHMA concentrations were proportionally higher at lower pH and results for anonymous urine samples varied widely among the methods. The method with the neutral preparation pH yielded results about 60% lower than the method using the most acidic conditions. Samples spiked with PHMA showed little variation, suggesting that the variability in results in human urine samples across methods is driven by the acid-mediated conversion of pre-PHMA to PHMA.

Volatile organic compounds (VOCs) are ubiquitous in the environment. In the United States (U.S.), tobacco smoke is the major non-occupational source of exposure to many harmful VOCs. Exposure to VOCs can be assessed by measuring their urinary metabolites (VOCMs). The Population Assessment of Tobacco and Health (PATH) Study is a U.S. national longitudinal study of tobacco use in the adult and youth civilian non-institutionalized population. We measured 20 VOCMs in urine specimens from a subsample of adults in Wave 1 (W1) (2013-2014) to characterize VOC exposures among tobacco product users and non-users. We calculated weighted geometric means (GMs) and percentiles of each VOCM for exclusive combustible product users (smokers), exclusive electronic cigarette (e-cigarette) users, exclusive smokeless product users, and tobacco product never users. We produced linear regression models for six VOCMs with sex, age, race, and tobacco user group as predictor variables. Creatinine-ratioed levels of VOCMs from exposure to acrolein, crotonaldehyde, isoprene, acrylonitrile, and 1,3-butadiene were significantly higher in smokers than in never users. Small differences of VOCM levels among exclusive e-cigarette users and smokeless users were observed when compared to never users. Smokers showed higher VOCM concentrations than e-cigarette, smokeless, and never users. Urinary VOC metabolites are useful biomarkers of exposure to harmful VOCs.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

BACKGROUND: Comprehensive information on the effect of time and temperature storage on the measurement of elements in human, whole blood (WB) by inductively coupled plasma-dynamic reaction cell-mass spectrometry (ICP-DRC-MS) is lacking, particularly for Mn and Se. METHODS: Human WB was spiked at 3 concentration levels, dispensed, and then stored at 5 different temperatures: -70 degrees C, -20 degrees C, 4 degrees C, 23 degrees C, and 37 degrees C. At 3 and 5weeks, and at 2, 4, 6, 8, 10, 12, 36months, samples were analyzed for Pb, Cd, Mn, Se and total Hg, using ICP-DRC-MS. We used a multiple linear regression model including time and temperature as covariates to fit the data with the measurement value as the outcome. We used an equivalence test using ratios to determine if results from the test storage conditions, warmer temperature and longer time, were comparable to the reference storage condition of 3weeks storage time at -70 degrees C. RESULTS: Model estimates for all elements in human WB samples stored in polypropylene cryovials at -70 degrees C were equivalent to estimates from samples stored at 37 degrees C for up to 2months, 23 degrees C up to 10months, and -20 degrees C and 4 degrees C for up to 36months. Model estimates for samples stored for 3weeks at -70 degrees C were equivalent to estimates from samples stored for 2months at -20 degrees C, 4 degrees C, 23 degrees C and 37 degrees C; 10months at -20 degrees C, 4 degrees C, and 23 degrees C; and 36months at -20 degrees C and 4 degrees C. This equivalence was true for all elements and pools except for the low concentration blood pool for Cd. CONCLUSIONS: Storage temperatures of -20 degrees C and 4 degrees C are equivalent to -70 degrees C for stability of Cd, Mn, Pb, Se, and Hg in human whole blood for at least 36months when blood is stored in sealed polypropylene vials. Increasing the sample storage temperature from -70 degrees C to -20 degrees C or 4 degrees C can lead to large energy savings. The best analytical results are obtained when storage time at higher temperature conditions (e.g. 23 degrees C and 37 degrees C) is minimized because recovery of Se and Hg is reduced. Blood samples stored in polypropylene vials also lose volume over time and develop clots at higher temperature conditions (e.g., 23 degrees C and 37 degrees C), making them unacceptable for elemental testing after 10months and 2months, respectively.

We improved our inductively coupled plasma mass spectrometry (ICP-MS) whole blood method [1] for determination of lead (Pb), cadmium (Cd), and mercury (Hg) by including manganese (Mn) and selenium (Se), and expanding the calibration range of all analytes. The method is validated on a PerkinElmer (PE) ELAN® DRC II ICP-MS (ICP-DRC-MS) and uses the Dynamic Reaction Cell (DRC) technology to attenuate interfering background ion signals via ion-molecule reactions. Methane gas (CH4) eliminates background signal from 40Ar2 + to permit determination of 80Se+, and oxygen gas (O2) eliminates several polyatomic interferences (e.g. 40Ar15N+, 54Fe1H+) on 55Mn+. Hg sensitivity in DRC mode is a factor of two higher than vented mode when measured under the same DRC conditions as Mn due to collisional focusing of the ion beam. To compensate for the expanded method's longer analysis time (due to DRC mode pause delays), we implemented an SC4-FAST autosampler (ESI Scientific, Omaha, NE), which vacuum loads the sample onto a loop, to keep the sample-to-sample measurement time to less than 5 min, allowing for preparation and analysis of 60 samples in an 8-h work shift. The longer analysis time also resulted in faster breakdown of the hydrocarbon oil in the interface roughing pump. The replacement of the standard roughing pump with a pump using a fluorinated lubricant, Fomblin®, extended the time between pump maintenance. We optimized the diluent and rinse solution components to reduce carryover from high concentration samples and prevent the formation of precipitates. We performed a robust calculation to determine the following limits of detection (LOD) in whole blood: 0.07 µg dL−1 for Pb, 0.10 µg L−1 for Cd, 0.28 μg L−1 for Hg, 0.99 µg L−1 for Mn, and 24.5 µg L−1 for Se. © 2016