Development and application of SPME technologies for the rapid sampling and analysis of anthropogenic compounds in the environment

Due to the wide spread use of pharmaceuticals in both human and animal populations, the contamination of surface waters resulting from the outflow of waste water treatment facilities is of growing concern. Conventional methods used for the determination of these compounds often require extensive sample preparation in order to achieve appropriate limits of detection and quantitation. As a result, analytical methods which utilize these procedures are limited in their throughput capacity, while also generating large volumes of solvent waste. Coated blade spray (CBS) is a solid phase microextraction (SPME) technique which enables the direct to mass spectrometry analysis of extracted compounds with the application of limited organic solvent in order to desorb analyte and perform electrospray ionization. Demonstrated herein is the application of CBS for the concomitant MS/MS analysis of 12 pharmaceuticals in environmental waters which was able to demonstrate LODs for all compounds at concentrations of less than 50 ng/L while employing a 30 second analysis time. As select pharmaceuticals are susceptible to bioaccumulation, the analysis of fish tissue as a marker of environmental pollution is also an area of interest. For this reason a device was developed, the SPME needle, which is able to perform rapid tissue analysis without the need for a protective sheathing needle or house, simplifying the sampling process. The device was further validated to be reproducible and not effected by puncture through protective tissue. Finally, the device was incorporated into a projectile which was validated to enable rapid one handed SPME sampler administration in a matter of seconds in an on-site proof of concept

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

Introducing a mechanically robust SPME sampler for the on-site sampling and extraction of a wide range of untargeted pollutants in environmental waters

The final publication is available at Elsevier via https://doi.org/10.1016/j.envpol.2019.06.013. © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The present study introduces a mechanically robust, sealable SPME sampler for the on-site sampling and extraction of a wide range of untargeted pollutants in environmental waters. Spray-coating and dip coating methodologies were used to coat the surfaces of six stainless steel bolts with a layer of HLB/PAN particles, which served as the extractive substrate in the proposed device. In addition, this sampler was designed to withstand rough handling, long storage times, and various environmental conditions. In order to identify whether the sampler was able to stabilize extracted compounds for long periods of time, the effects of storage time and temperature were evaluated. The results of these tests showed no significant differences in the quantity and quality of the extracted chemicals following 12 days storage at room temperature, thus confirming the device's suitability for use at sampling sites that are far away from the laboratory facilities. The proposed device was also used to perform extraction and untargeted analyses of river waters in five different geographical locations. The constituent chemicals in the samplers were analyzed and determined using high-resolution HPLC-Orbitrap MS. Toxin and Toxin-Target Database was used as a reference database for toxins and environmental contaminants. Ultimately, over 80 tentative chemicals with widely varying hydrophobicities ranging within −2.43 < logP <11.9—including drugs, metabolites, wide ranges of toxins, pesticide, and insecticides—were identified in the samplers used in the different rivers. The log P values for the tentative analytes confirmed that the introduced device is suitable for the extraction and trace analysis of wide ranges of targeted and untargeted pollutants.The authors would also like to thank the Natural Sciences and Engineering Research Council of Canada (NSERC) for financial support. Water sampling in China was performed during visit at Lehn Institute of Functional Materials (LIFM), Sun Yat-sen University supported by the 111 project (90002- 18011002)

Solid Phase Microextraction On-Fiber Derivatization Using a Stable, Portable, and Reusable Pentafluorophenyl Hydrazine Standard Gas Generating Vial

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 publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.analchem.6b01449Solid phase microextraction (SPME) on-fiber derivatization methods have facilitated the achievement of lower detection limits and targeted analysis of various substances that exhibit poor chromatographic behavior, thermal instability, or high reactivity while limiting the use of organic solvents. However, previously developed on-fiber derivatization methods have been hindered by poor loading reproducibility and standard lifetime due to derivatization reagent reactivity. In addition, this reactivity often results in these reagents demonstrating toxic effects, complicating handling and standard formulation. To address this, a reusable standard gas generating vial containing pentafluorophenyl hydrazine (PFPH) has been developed. With this development, SPME fibers can now be reproducibly loaded with derivatization reagent, from an easy to use and safe platform. Validation of the vial using C-4-C-9 linear aldehyde standards as target analytes demonstrated intrabatch vial reproducibility (2% relative standard deviation (RSD), n = 4), along with PFPH headspace stability over a period of 11 weeks, facilitating reduced reagent consumption due to standard longevity. In addition, reproducibility of the derivatization reaction was observed over 1 week (RSD 0.996, 10-200 ppb v/v). Finally, the PFPH-generating vial was applied to the monitoring of volatile aldehydes generated during meat spoilage, as well as an on-site application where the free and total concentration of formaldehyde was determined in car exhaust using a portable GC/MS. To the best of our knowledge, the standard gas generating vial proposed in this work is the first documented device for the long-term storage of reusable headspace standards for a reactive, toxic, and otherwise unstable derivatization reagent standard.Natural Science and Engineering Research Council of CanadaSupelcoTorion Technologies of PerkinElmer Inc.Torion Technologies of Perkin Elmer Co

Solid Phase Microextraction On-Fiber Derivatization Using a Stable, Portable, and Reusable Pentafluorophenyl Hydrazine Standard Gas Generating Vial

Solid phase microextraction (SPME) on-fiber derivatization methods have facilitated the achievement of lower detection limits and targeted analysis of various substances that exhibit poor chromatographic behavior, thermal instability, or high reactivity while limiting the use of organic solvents. However, previously developed on-fiber derivatization methods have been hindered by poor loading reproducibility and standard lifetime due to derivatization reagent reactivity. In addition, this reactivity often results in these reagents demonstrating toxic effects, complicating handling and standard formulation. To address this, a reusable standard gas generating vial containing pentafluorophenyl hydrazine (PFPH) has been developed. With this development, SPME fibers can now be reproducibly loaded with derivatization reagent, from an easy to use and safe platform. Validation of the vial using C₄–C₉ linear aldehyde standards as target analytes demonstrated intrabatch vial reproducibility (2% relative standard deviation (RSD), <i>n</i> = 4), along with PFPH headspace stability over a period of 11 weeks, facilitating reduced reagent consumption due to standard longevity. In addition, reproducibility of the derivatization reaction was observed over 1 week (RSD < 9%), and the linear concentration range was evaluated using headspace extractions from aqueous aldehyde solutions (<i>R</i>² > 0.996, 10–200 ppb v/v). Finally, the PFPH-generating vial was applied to the monitoring of volatile aldehydes generated during meat spoilage, as well as an on-site application where the free and total concentration of formaldehyde was determined in car exhaust using a portable GC/MS. To the best of our knowledge, the standard gas generating vial proposed in this work is the first documented device for the long-term storage of reusable headspace standards for a reactive, toxic, and otherwise unstable derivatization reagent standard

Simultaneous Determination of Immunosuppressive Drugs from Whole Blood by CoatedBlade Spray Ionization-Mass Spectrometry

Coated Blade Spray (CBS) ionization was conceived as a fast and simple sampling/sample-preparation and ionization method for qualitative/quantitative mass spectrometry (MS) analysis of drugs of abuse, pharmaceuticals, and other small molecules from urine, blood, and other biofluids. This study describes the use of the CBS for the quantitation of immunosuppressive drugs from 100 µL of blood samples, focusing specifically on the simultaneous quantitation of everolimus, tacrolimus, sirolimus, and cyclosporine-A. These drugs are characterized for having a narrow therapeutic range (e.g. 2-15 ng mL-1, 5-15 ng mL-1, 6-8 ng mL-1, and 100-350 ng mL-1 for tacrolimus (TAC), sirolimus (SIR), everolimus (EVR) and cyclosporine A (CycA), respectively); therefore, continuous monitoring to avoid either subtherapeutic or toxic effect is always required. Our results showed rewarding limits of quantitation (1 ng mL-1 for EVR/SIR/TAC, and 10 ng mL-1 for CycA) as well as good accuracy (• 90 %) and linearity (R2>0.99) over the range evaluated for all the compounds (1-50 ng/mL for EVR/SIR/TAC, and 10-500 ng mL-1 for CycA). The precision of the method was below 15% in all the cases and the bias for three different validation points ranged from 2% to 10%. No matrix effects were observed when evaluating this methodology at different hematocrit levels. By using a high-throughput autosampler, a total analysis time of less than 3 minutes can be attained per sample