Development of a Carbon Mesh Supported Thin Film Microextraction Membrane As a Means to Lower the Detection Limits of Benchtop and Portable GC/MS Instrumentation

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.analchem.5b04008.In this work, a durable and easy to handle thin film microextraction (TFME) device is reported. The membrane is comprised of poly(divinylbenzene) (DVB) resin particles suspended in a high-density polydimethylsiloxane (PDMS) glue, which is spread onto a carbon fiber mesh. The currently presented membrane was shown to exhibit a substantially lesser amount of siloxane bleed during thermal desorption, while providing a statistically similar extraction efficiency toward a broad spectrum of analytes varying in polarity when compared to an unsupported DVB/PDMS membrane of similar shape and size which was prepared with previously published methods. With the use of hand-portable GC-TMS instrumentation, membranes cut with dimensions 40 mm long by 4.85 mm wide and 40 ± 5 μm thick (per side) were shown to extract 21.2, 19.8, 18.5, 18,4, 26.8, and 23.7 times the amount of 2,4 dichlorophenol, 2,4,6 trichlorophenol, phorate D10, fonofos, chloropyrifos, and parathion, respectively, within 15 min from a 10 ppb aqueous solution as compared to a 65 μm DVB/PDMS solid phase microextraction (SPME) fiber. A portable high volume desorption module prototype was also evaluated and shown to be appropriate for the desorption of analytes with a volatility equal to or lesser than benzene when employed in conjunction with TFME membranes. Indeed, the coupling of these TFME devices to hand-portable gas chromatography toroidial ion trap mass spectrometry (GC-TMS) instrumentation was shown to push detection limits for these pesticides down to the hundreds of ppt levels, nearing that which can be achieved with benchtop instrumentation. Where these membranes can also be coupled to benchtop instrumentation it is reasonable to assume that detection limits could be pushed down even further. As a final proof of the concept, the first ever, entirely on-site TFME-GC-TMS analysis was performed at a construction impacted lake. Results had indicated the presence of contaminants such as toluene, ethylbenzene, xylene, 2,2,4-trimethyl-1,3-pentanediol diisobutyrate, and tris(1-chloro-2-propyl)phosphate, which stood out from other naturally occurring compounds detected.the Natural Sciences and Engineering Research Council of Canada (NSERC

Poly(3-alkylthiophenes): new sorption materials for solid phase microextraction of drugs isolated from human plasma

A novel sorbent in solid phase microextraction (SPME) method based on poly(3-alkylthiophenes) was used in the isolation of linezolid from human plasma samples following liquid chromatography determination. The effect of extraction time on the sorption capacity of the SPME process was studied and pointed at 10 min both for adsorption and desorption. Poly(3-methylthiophene) and poly(3-nonylthiophene) were applied for the extraction of linezolid from water solutions. In plasma samples, four coatings including polythiophene and poly(3-penthylthiophene) were investigated. With these measurements, correlation coefficients were calculated in the range from 0.9820 to 0.9995, and the relative standard deviations were below 15%. That allowed claiming that the synthesized and described materials can be successfully applied in the analysis of linezolid also from other matrices such as urine or blood

Monitoring of oxidative and metabolic stress during cardiac surgery by means of breath biomarkers: an observational study

Research articl

Development and validation of eco-friendly strategies based on thin film microextraction for water analysis

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.chroma.2018.10.026 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/The aim of the current study is the establishment of Green Analytical Chemistry strategies for water analysis by elimination/reduction of hazardous chemicals, energy consumption, and waste generation throughout the entire analytical workflow. The first approach introduced in this manuscript consists of addition of water to a sampling vessel that contains a thin film microextraction (TFME) device, followed by removal of the device after equilibration, and subsequent quantification of the extracted components by thermal desorption GC/MS. In this approach, namely the in-bottle TFME approach, analyte-loss associated errors that stem from analyte adherence to glass surfaces and/or degradation are avoided as extraction occurs in situ, while analytes are isolated from a complex matrix that contains degradation agents (bacteria, oxidizing or reducing species, etc.). This procedure also circumvents the splitting of original samples into sub-samples. The second approach involves the use of portable TFME devices that facilitate on-site extraction of compounds, therefore eliminating the use of collection vessels, a factor known to potentially introduce errors into analysis. The herein described procedure involves attachment of the TFME device to drill accessories, analyte extraction via direct immersion into sampled site, and subsequent on-site instrumental analysis, which is carried out with the use of a portable GC/MS containing an appropriate thermal desorption interface, or alternatively, by transferring the membrane to the laboratory for bench-top GC/MS analysis. To facilitate a better understanding of the processes governing the developed approaches, modeling by COMSOL Multiphysics® software was performed. The findings of this study were applied for further method optimization, and the optimized developed methods were then applied for on-site surface water analyses. Finally, the greenness of the developed methods was evaluated with use of the eco-scale assessment, with obtained scores compared to that of the US EPA 8270 method.Ontario Research FundMaxxam Analytics (Mississagua, ON

Rapid determination of immunosuppressive drug concentrations in whole blood by coated blade spray-tandem mass spectrometry (CBS-MS/MS)

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.aca.2017.10.016 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Coated Blade Spray (CBS) is a technology that efficiently integrates sample preparation and direct coupling to mass spectrometry (MS) on a single device. In this article, we present CBS-tandem mass spectrometry (CBS-MS/MS) as a novel tool for the rapid and simultaneous determination of four commonly used immunosuppressive drugs (ISDs) in whole blood: tacrolimus (TAC) and cyclosporine-A (CycA), which are calcineurin inhibitors; and sirolimus (SIR) and everolimus (EVR), which are both mTOR (mechanistic target of rapamycin) inhibitors. Given that CBS extracts via free concentration, analytes that are largely bound to plasma proteins or red blood cells provide considerably lower extraction recovery rates. Therefore, we defy the solventless philosophy of SPME-based techniques, like CBS, by performing the analyte-enrichment step via direct immersion in a solvent-modified matrix. The assay was linear within the evaluated range of concentrations (between 1 and 100 ng/mL for EVR/SIR/TAC and 10–1000 ng/mL for CycA), and the limits of quantification were determined to be 10 ng/mL for CycA and 1 ng/mL for EVR/SIR/TAC. Good accuracy (87–119%) and linearity (r2 ≥ 0.99) were attained over the evaluated range for all ISDs. Interassay imprecision (CV) determined from incurred sample reanalysis was ≤10% for all ISDs. Our method was validated using Liquichek™ whole blood immunosuppressant quality control (QC) standards purchased from Bio-Rad. Concentrations determined by CBS-MS/MS were inside the range specified by Bio-Rad and within 15% of the expected mean value for all ISDs at all QC levels. Furthermore, the effect of different hematocrit levels (20, 45, and 70%) in the entire calibration range was carefully studied. No statistical differences (RSD ≤ 7%) in the calibration curve slopes of ISDs in blood were observed. CBS offers a simpler workflow than that of traditional methods; it eliminates the need for chromatographic separation and provides a clean extract that allows for long-term MS instrumental operation with minimal maintenance. Additionally, because CBS integrates all analytical steps into one device, it eliminates the risk of instrumental carry-over and can be used as a low-cost disposable device for sample preparation and analysis. Fully-automated sample preparation simplifies the method and allows for total analysis times as short as 3 min with turn-around times of less than 90 min.Natural Sciences and Engineering Research Council of Canada (NSERC) Industrial Research Chair progra

Quantitative analysis of biofluid spots by coated blade spray mass spectrometry, a new approach to rapid screening

This study demonstrates the quantitative capabilities of coated blade spray (CBS) mass spectrometry (MS) for the concomitant analysis of multiple target substances in biofluid spots. In CBS-MS the analytes present in a given sample are first isolated and enriched in the thin coating of the CBS device. After a quick rinsing of the blade surface, as to remove remaining matrix, the analytes are quickly desorbed with the help of a solvent and then directly electrosprayed into the MS analyzer. Diverse pain management drugs, controlled substances, and therapeutic medications were successfully determined using only 10 µL of biofluid, with limits of quantitation in the low/sub ng·mL−1 level attained within 7 minutes.Thermo Scientific Natural Sciences and Engineering Research Council (NSERC) of Canada - Industrial Research Chair program Authors are very grateful with Pfizer Canada Inc., Merck Canada Inc., Quebec Consortium for Drug Discovery (CQDM), Brain Canada, and Ontario Brain Institute for the grant “Solid phase microextraction-based integrated platform for untargeted and targeted in vivo brain studies

Solid-Phase Microextraction and the Human Fecal VOC Metabolome

The diagnostic potential and health implications of volatile organic compounds (VOCs) present in human feces has begun to receive considerable attention. Headspace solid-phase microextraction (SPME) has greatly facilitated the isolation and analysis of VOCs from human feces. Pioneering human fecal VOC metabolomic investigations have utilized a single SPME fiber type for analyte extraction and analysis. However, we hypothesized that the multifarious nature of metabolites present in human feces dictates the use of several diverse SPME fiber coatings for more comprehensive metabolomic coverage. We report here an evaluation of eight different commercially available SPME fibers, in combination with both GC-MS and GC-FID, and identify the 50/30 µm CAR-DVB-PDMS, 85 µm CAR-PDMS, 65 µm DVB-PDMS, 7 µm PDMS, and 60 µm PEG SPME fibers as a minimal set of fibers appropriate for human fecal VOC metabolomics, collectively isolating approximately 90% of the total metabolites obtained when using all eight fibers. We also evaluate the effect of extraction duration on metabolite isolation and illustrate that ex vivo enteric microbial fermentation has no effect on metabolite composition during prolonged extractions if the SPME is performed as described herein

GC–MS and GC–NPD Determination of Formaldehyde Dimethylhydrazone in Water Using SPME

Formaldehyde dimethylhydrazone (FADMH) is one of the important transformation products of residual rocket fuel 1,1-dimethylhydrazine (1,1-DMH). Thus, recent studies show that FADMH toxicity is comparable to that of undecomposed 1,1-DMH. In this study, a new method for quantification of FADMH in water based on solid phase microextraction (SPME) in combination with gas chromatography (GC) with mass spectrometric (MS) and nitrogen-phosphorus detection (NPD) is presented. Effects of SPME fiber coating type, extraction and desorption temperatures, extraction time, and pH on analyte recovery were studied. The optimized method used 65 micron polydimethylsiloxane/divinylbenzene fiber coating for 1 min headspace extractions at 30 °C. Preferred pH and desorption temperature from the SPME fiber are >8.5 and 200 °C, respectively. Detection limits were estimated to be 1.5 and 0.5 μg L−1 for MS and NPD, respectively. The method was applied to laboratory-scale experiments to quantify FADMH. Results indicate applicability for in situ sampling and analysis and possible first-time detection of free FADMH in water

Major liver resection, systemic fibrinolytic activity, and the impact of tranexamic acid

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.hpb.2016.09.005 © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Background: Hyperfibrinolysis may occur due to systemic inflammation or hepatic injury that occurs during liver resection. Tranexamic acid (TXA) is an antifibrinolytic agent that decreases bleeding in various settings, but has not been well studied in patients undergoing liver resection. Methods: In this prospective, phase II trial, 18 patients undergoing major liver resection were sequentially assigned to one of three cohorts: (i) Control (no TXA); (ii) TXA Dose I - 1 g bolus followed by 1 g infusion over 8 h; (iii) TXA Dose II - 1 g bolus followed by 10 mg/kg/hr until the end of surgery. Serial blood samples were collected for thromboelastography (TEG), coagulation components and TXA concentration. Results: No abnormalities in hemostatic function were identified on TEG. PAP complex levels increased to peak at 1106 mu g/L (normal 0-512 mu g/L) following parenchymal transection, then decreased to baseline by the morning following surgery. TXA reached stable, therapeutic concentrations early in both dosing regimens. There were no differences between patients based on TXA. Conclusions: There is no thromboelastographic evidence of hyperfibrinolysis in patients undergoing major liver resection. TXA does not influence the change in systemic fibrinolysis; it may reduce bleeding through a different mechanism of action