Lipid hydroperoxides are important products of enzymatic processes and autooxidation products of polyunsaturated fatty acids. Analysis of such compounds has proved difficult in the past, but negative ion electrospray ionization mass spectrometry was found to be suitable for direct analysis. Abundant [M - H](-) ions were observed in full scan mode for hydroper-oxyeicosatetraenoic (HPETE), hydroperoxyoctadecenoic acid isomers, and 5,12-diHPETE. Loss of water was observed for all species. Collisional activation and tandem mass spectrometry generated unique and characteristic spectra that shared some common features such as loss of small neutral molecules. More importantly, fragment ions that were indicative of the position of the hydroperoxide were observed. Collision-induced decomposition (CID) of [M - H2O](-) for the HPETE isomers was found to be virtually identical to the CID mass spectra of the [M - H](-) anions from corresponding keto-eicosatetraenoic acids, which suggests that the hydroperoxide anions decompose via a dehydration intermediate that resembles the keto acid molecular anion. Cleavage of the double bond allylic to the hydroperoxide formed structurally characteristic ions at m/z 129 from 5-HPETE, m/z 153 from 12-HPETE, and m/z 113 from 15-HPETE. Charge-driven allylic fragmentation led to formation of m/z 203 from 5-HPETE, m/z 179 from 12-HPETE, and m/z 219 from 15-HPETE. Mechanisms consistent with the decomposition of stable isotope analogues are proposed for the formation of these and other characteristic ions. These specific decompositions can be used in multiple reaction monitoring to measure picomolar concentrations of hydroperoxides by direct high performance liquid chromatography tandem mass spectrometry.

Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo TK data available to benchmark these methods are from pharmaceuticals. Here we report on new, in vivo rat TK experiments for 26 non-pharmaceutical chemicals with environmental relevance. Both intravenous and oral dosing were used to calculate bioavailability. These chemicals, and an additional 19 chemicals (including some pharmaceuticals) from previously published in vivo rat studies, were systematically analyzed to estimate in vivo TK parameters (e.g., volume of distribution [Vd], elimination rate). For each of the chemicals, rat-specific HTTK data were available and key TK predictions were examined: oral bioavailability, clearance, Vd, and uncertainty. For the non-pharmaceutical chemicals, predictions for bioavailability were not effective. While no pharmaceutical was absorbed at less than 10%, the fraction bioavailable for non-pharmaceutical chemicals was as low as 0.3%. Total clearance was generally more under-estimated for nonpharmaceuticals and Vd methods calibrated to pharmaceuticals may not be appropriate for other chemicals. However, the steady-state, peak, and time-integrated plasma concentrations of nonpharmaceuticals were predicted with reasonable accuracy. The plasma concentration predictions improved when experimental measurements of bioavailability were incorporated. In summary, HTTK and IVIVE methods are adequately robust to be applied to high throughput in vitro toxicity screening data of environmentally relevant chemicals for prioritizing based on human health risks.

Mitoxantrone is an anticancer agent for which it is important to know the concentration in blood during therapy. Current methods of analysis are cumbersome, requiring a pretreatment stage. A method based on surface-enhanced resonance Raman scattering (SERRS) has been developed using a flow cell and silver colloid as the SERRS substrate. It is simple, sensitive, fast, and reliable. Both blood plasma and serum can be analyzed directly, but fresh serum is preferred here due to reduced fluorescence in the clinical samples available. Fluorescence is reduced further by the dilution of the serum in the flow cell and by quenching by the silver of surface-adsorbed material. The effectiveness of the latter process is dependent on the contact time between the serum and the silver. The linear range encompasses the range of concentrations detected previously in patient samples using HPLC methods. In a comparative study of a series of samples taken from a patient at different times, there is good agreement between the results obtained by HPLC and SERRS with no significant difference between them at the 95% limit. The limit of detection in serum using the final optimized procedure for SERRS was 4.0 x 10(-11) M (0.02 ng/mL) mitoxantrone. The ease with which the SERRS analysis can be carried out makes it the preferred choice of technique for mitoxantrone analysis.

Previous research has reported concurrent levels of pyrethroid insecticides and their environmental degradates in foods. These data raise concerns about using these same pyrethroid degradates found in the diet as urinary biomarkers of exposures in humans. The primary objective was to quantify levels of selected pyrethroids and their environmental degradates in duplicate-diet solid food samples of 50 adults over a six-week monitoring period. The study was conducted at the US EPA’s Human Studies Facility in North Carolina and at participants’ residences in 2009–2011. Participants collected duplicate-diet solid food samples on days 1 and 2 during weeks 1, 2, and 6 of the monitoring period. These samples were collected over three consecutive time periods each sampling day. A total of 782 food samples were homogenized and analyzed by LC/MS/MS for seven pyrethroids (bifenthrin, λ-cyhalothrin, cyfluthrin, cypermethrin, cis-deltamethrin, esfenvalerate, and cis/trans-permethrin) and six pyrethroid degradates. Results showed that 49% and 2% of all the samples contained at least one target pyrethroid or pyrethroid degradate, respectively. Cis/trans-permethrin (20%) and bifenthrin (20%) were the most frequently detected pyrethroids. The results suggest that the pyrethroid degradates were likely not present in sufficient levels in the diet to substantially impact the adults’ urinary biomarker concentrations.