Feasibility of basic transesophageal echocardiography in hemorrhagic shock: potential applications during resuscitative endovascular balloon occlusion of the aorta (REBOA).

BACKGROUND: There are numerous studies in the cardiovascular literature that have employed transesophageal echocardiography (TEE) in swine models, but data regarding the use of basic TEE in swine models is limited. The primary aim of this study is to describe an echocardiographic method that can be used with relative ease to qualitatively assess cardiovascular function in a porcine hemorrhagic shock model using resuscitative endovascular balloon occlusion of the aorta (REBOA). METHODS: Multiplane basic TEE exams were performed in 15 during an experimental hemorrhage model using REBOA. Cardiac anatomical structure and functional measurements were obtained. In a convenience sample (two animals from each group), advanced functional cardiovascular measurements were obtained before and after REBOA inflation for comparison with qualitative assessments. RESULTS: Basic TEE exams were performed in 15 swine. Appropriate REBOA placement was confirmed using TEE in all animals and verified with fluoroscopy. Left ventricular volume was decreased in all animals, and left ventricular systolic function increased following REBOA inflation. Right ventricular systolic function and volume remained normal prior to and after hemorrhage and REBOA use. Mean ejection fraction (EF) decreased from 64% (S.D. 9.6) to 62.1 (S.D. 16.8) after hemorrhage and REBOA inflation (p = 0.76); fractional area of change (FAC) decreased from 49.8 (S.D. 9.0) to 48.5 (S.D. 13.6) after hemorrhage and REBOA inflation (p = 0.82). CONCLUSION: Basic TEE, which requires less training than advanced TEE, may be employed by laboratory investigators and practitioners across a wide spectrum of experimental and clinical settings.

A multidisciplinary approach for the analysis of an adulterated dietary supplement where the active pharmaceutical ingredient was embedded in the capsule shell.

Fourier transform infrared (FT-IR) microspectroscopic imaging, Raman microspectroscopy, optical microscopy and high performance liquid chromatography with mass spectrometric (LC/MS) detection were employed to examine a dietary supplement adulterated with an undeclared active pharmaceutical ingredient (API). While a trace level of the API was detected in the capsule contents, a higher concentration of API was found in the capsule shell, which indicated the use of an unconventional manufacturing process to hide the API and thus avoid detection. This study demonstrates the need for a multidisciplinary approach to provide a complete assessment of a suspect adulterated dietary supplement.

Screening and determination of polycyclic aromatic hydrocarbons in seafoods using QuEChERS-based extraction and high-performance liquid chromatography with fluorescence detection.

A rapid, sensitive, and accurate method for the screening and determination of polycyclic aromatic hydrocarbons (PAHs) in edible seafood is described. The method uses quick, easy, cheap, effective, rugged, and safe (QuEChERS)-based extraction and HPLC with fluorescence detection (FLD). The method was developed and validated in response to the massive Deepwater Horizon oil spill in the Gulf of Mexico. Rapid and highly sensitive PAH screening methods are critical tools needed for oil spill response; they help to assess when seafood is safe for harvesting and consumption. Sample preparation involves SPE of edible seafood portions with acetonitrile, followed by the addition of salts to induce water partitioning. After centrifugation, a portion of the acetonitrile layer is filtered prior to analysis via HPLC-FLD. The chromatographic method uses a polymeric C18 stationary phase designed for PAH analysis with gradient elution, and it resolves 15 U.S. Environmental Protection Agency priority parent PAHs in fewer than 20 min. The procedure was validated in three laboratories for the parent PAHs using spike recovery experiments at PAH fortification levels ranging from 25 to 10 000 microg/kg in oysters, shrimp, crab, and finfish, with recoveries ranging from 78 to 99%. Additional validation was conducted for a series of alkylated homologs of naphthalene, dibenzothiophene, and phenanthrene, with recoveries ranging from 87 to 128%. Method accuracy was further assessed based on analysis of National Institute of Standards and Technology Standard Reference Material 1974b. The method provides method detection limits in the sub to low ppb (microg/kg) range, and practical LOQs in the low ppb (microg/kg) range for most of the PAH compounds studied.

Surface swabbing technique for the rapid screening for pesticides using ambient pressure desorption ionization with high-resolution mass spectrometry.

A rapid screening method for pesticides has been developed to promote more efficient processing of produce entering the United States. Foam swabs were used to recover a multiclass mixture of 132 pesticides from the surfaces of grapes, apples, and oranges. The swabs were analyzed using direct analysis in real time (DART) ionization coupled with a high-resolution Exactive Orbitrap™ mass spectrometer. By using a DART helium temperature gradient from 100-350°C over 3 min, a minimal separation of analytes based on volatility differences was achieved. This, combined with the Exactive's mass resolution of 100,00, allowed the chromatographic step, along with the typical compositing and extraction steps associated with gas chromatography/mass spectrometry (GC/MS) or liquid chromatography/mass spectrometry (LC/MS) approaches, to be eliminated. Detection of 86% of the analytes present was consistently achieved at levels of 2 ng/g (per each apple or orange) and 10 ng/g (per grape). A resolution study was conducted with four pairs of isobaric compounds analyzed at a mass resolution of 100 000. Baseline separation was achieved with analyte ions differing in mass by 25 ppm and analyte ions with a mass difference of 10 ppm were partially resolved. In addition, field samples that had undergone traditional sample preparation using QuEChERS (quick, easy, cheap, rugged, and safe) were analyzed using both LC/MS and DART-MS and the results from the two techniques were found to be comparable in terms of identification of the pesticides present. The use of swabs greatly increased sample throughput by reducing sample preparation and analysis time.

Accurate mass measurement using Fourier transform ion cyclotron resonance mass spectrometry for structure elucidation of designer drug analogs of tadalafil, vardenafil and sildenafil in herbal and pharmaceutical matrices.

Phosphodiesterase type 5 (PDE-5) inhibitors are a class of drugs used primarily in the treatment of erectile dysfunction. The Food and Drug Administration (FDA) approved PDE-5 inhibitors include sildenafil citrate, vardenafil hydrochloride and tadalafil. In this study, accurate mass measurements were made by electrospray ionization (ESI) using Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) to elucidate the structures of sildenafil, tadalafil and vardenafil analogs that were found in products marketed as dietary supplements. Initial detection of these analogs was accomplished through routine screening of suspect samples by liquid chromatography/electrospray ionization multi-stage mass spectrometry (LC/ESI-MS(n)) on a low-resolution ion trap instrument. The chromatographic behavior and mass spectrometric fragmentation patterns observed were often similar to those observed for FDA approved PDE-5 inhibitors. The mass accuracy and resolving power associated with FTICRMS allows for the determination of elemental compositions. Elucidation of the product ion structures for the analogs was accomplished through the use of accurate mass measurements with the aid of Mass Frontier software (version 4.0). Using FTICRMS, accurate masses with measurement errors averaging <0.4 ppm were achieved, allowing assignment of one possible elemental formula to each fragment ion. The mass measurement errors associated with [M + H](+) for the analogs aminotadalafil, piperidino vardenafil, hydroxyacetildenafil and piperidino acetildenafil were 0.1, 0.0, 0.1 and 0.5 ppm, respectively. Based on the accuracy of the measurements, structural assignments could be made with a high degree of confidence.

Preservation of As(III) and As(V) in drinking water supply samples from across the United States using EDTA and acetic acid as a means of minimizing iron-arsenic coprecipitation.

Seven different treatment/storage conditions were investigated for the preservation of the native As(III)/As(V) found in 10 drinking water supplies from across the United States. These 10 waters were chosen because they have different As(III)/As(V) distributions; six of these waters contained enough iron to produce an iron precipitate during shipment. The waters were treated and stored under specific conditions and analyzed periodically over a span of approximately 75 days. Linear least squares (LLS) was used to estimate the change in As(III) and As(V) over the study period. Point estimates for the first and last analyses days and 95% confidence bounds were calculated from the LLS. The difference in the point estimates for the first and last day were then evaluated with respect to drinking water treatment decision making. Three primary treatments were evaluated: EDTA/AcOH-treatment and AcOH treatment as well as no treatment. The effect of temperature was explored for all treatments, while the effect of aeration was evaluated for only the EDTA/AcOH treated samples. The nontreated samples experienced a 0-40% reduction in the native arsenic concentration due to the formation of Fe/As precipitates. The Fe/As precipitates were resolubilized and shown to contain elevated concentrations of As(V) relative to the native distribution. Once this Fe/As precipitate was removed from solution using a 0.45 and 0.2 microm filter, the resulting arsenic concentration (As(III) + As(V)) was relatively constant (the largest LLS slope was -1.4 x 10(-2) (ng As g water(-1)) day(-1)). The AcOH treatment eliminated the formation of the Fe/As precipitate observed in the nontreated samples. However, two of the AcOH water samples produced analytically significant changes in the As(III) concentration. The LLS slopes for these two waters were -5.7 x 10(-2) (ng As(III) g water(-1)) day(-1) and -1.0 x 10(-1) (ng As(III) g water(-1)) day(-1). This corresponds to a -4.3 ng/g and a -7.8 ng/g change in the As(III) concentration over the study period, which is a 10% shift in the native distribution. The third and final treatment was EDTA/AcOH. This treatment eliminated the Fe/As precipitate that formed in the nontreated sample. The LLS slopes were less than -7.5 x 10(-3) (ng As(III) g water(-1)) day(-1) for the above-mentioned waters, corresponding to a 0.6 ng/g change over the study period. One of the EDTA/AcOH treated waters did indicate that using the 5 degrees C storage temperature minimized the rate of conversion relative to 20 degrees C storage.

Simultaneous analysis of hepatotoxic pyrrolizidine alkaloids and N-oxides in comfrey root by LC-ion trap mass spectrometry.

The purpose of the current study was to develop a LC-MS(n) method for the analysis of pyrrolizidine alkaloids (PAs) in comfrey. Published data presents an extensive list of PAs and their N-oxides present in comfrey. However, standards are not commercially available for any of the PAs typically present in comfrey. Those PAs that are not stereoisomers were readily resolved on a C(18) column using a water-acetonitrile gradient as the mobile phase. The use of a selective technique, LC-MS/MS, allowed us to identify groups of PAs and their N-oxides, as well as identify the number of PAs present in each group, including those that were not completely resolved chromatographically.

An investigation of the chemical stability of arsenosugars in basic environments using IC-ICP-MS and IC-ESI-MS/MS.

This paper evaluates the chemical stability of four arsenosugars using tetramethylammonium hydroxide (TMAOH) as an extraction solvent. This solvent was chosen because of the near quantitative removal of these arsenicals from difficult to extract seafood (oysters and shellfish). Four arsenosugars (3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropylene glycol--As(328), 3-5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropanesulfonic acid--As(392), 3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropyl hydrogen sulfate--As(408), and 3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropyl-2,3-hydroxypropyl phosphate--As(482)) were evaluated. The stability of these four arsenosugars were studied independently in a solution of 2.5% TMAOH at 60 degrees C over a period of up to 8 h. Two arsenosugars, As(328) and As(392), were found to be relatively stable in this solution for up to 8 h. However, As(408) and As(482) formed detectable quantities of dimethylarsinic acid (DMAA) and As(328) within 0.5 and 2 h, respectively. It was found that 97% of As(408) degrades after 8 h of treatment producing 3.4 times as much DMAA as As(328). This is contrary to As(482), which produces 13 times as much As(328) as DMAA and only 37% of the As(482) was converted by the 8 h treatment at 60 degrees C. These degradation products led to the investigation of weaker TMAOH extraction solvents. Three different concentrations (2.5%, 0.83% and 0.25%) were used to determine the effect of TMAOH concentration on the degradation rate of As(408). By reducing the TMAOH concentration to 0.83%, the conversion of the arsenosugar to As(328) and DMAA is nearly eliminated (less than 5% loss). Arsenosugars, As(408) and As(482), were also studied in 253 mM NaOH to verify the degradation products. The NaOH experiments were conducted to investigate a possible hydroxide based reaction mechanism. Similar degradation plots were found for each arsenosugar when compared to the 2.5% TMAOH data. A mechanism has been proposed for the formation of As(328) from As(408) and As(482) in base via an SN2 reaction (hydroxide attack) at the side chain carbon adjacent to the inorganic ester. The formation of DMAA is observed in all arsenosugars after prolonged exposure. This probably occurs via an SN2 attack at the arsenic atom.

An investigation of the chemical stability of arsenosugars in simulated gastric juice and acidic environments using IC-ICP-MS and IC-ESI-MS/MS.

A more quantitative extraction of arsenic-containing compounds from seafood matrices is essential in developing better dietary exposure estimates. More quantitative extraction often implies a more chemically aggressive set of extraction conditions. However, these conditions may result in undesirable chemical changes in the native arsenicals which may further complicate the toxicological risk assessment. This balance between quantitative extraction and species-specific integrity may be best addressed by using simulated gastric juice as an extraction solvent to mimic 'bioavailability'. This, conceptually, should extract the bioavailable fraction and induce any chemical changes that would occur because of ingestion. The most chemically labile species associated with seafood are thought to be the arsenosugars and for this reason their chemical stability is investigated in this study. Four arsenosugars (3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropylene glycol, As(328); 3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropanesulfonic acid, As(392); 3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxyl-2-hydroxypropyl hydrogen sulfate, As(408); and 3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropyl-2,3-hydroxypropyl phosphate, As(482)) were isolated from seaweed extracts and subjected to simulated gastric juice and acidic conditions which mimic the stomach's pH of 1.1. Three acid solutions were used to test the chemical stability of the arsenosugars: simulated gastric juice, 78 mM nitric acid and 78 mM hydrochloric acid. The composition of the solutions was monitored over time (up to 48 h) using IC-ICP-MS for detection. The arsenosugars were found to degrade at the rate of 1.4% per h at 38 degrees C and 12.2% per h at 60 degrees C. The plots of percent conversion versus time were found to be independent of the starting arsenosugar and all had r2 values of greater than 0.97. A single common degradation product was observed in all the stability studies. A mass balance between the starting arsenosugar (As(392), As(408) and As(482)) and the degradation product was conducted with each set of experiments. This mass balance indicated that the degradation process did not produce any unchromatographable species. This degradation product was tentatively identified as As(254) as determined by ESI-MS/MS spectral data. An acid hydrolysis mechanism was proposed for the formation of As(254) from each of the native arsenosugars by hydrolysis at the C-1 carbon on the ribose ring.