Condensed Phase Membrane Introduction Mass Research Articles

Online Membrane Sampling for the Mass Spectrometric Analysis of Oil Sands Process Affected Water-Derived Naphthenic Acids in Real-World Samples

Large volumes of oil sands process-affected waters (OSPW) result from heavy oil extraction in Alberta, Canada. Currently, a toxic legacy of ca. 500 Mm3 is stored in tailings ponds under a zero-discharge policy. OSPW is a complex mixture of suspended and dissolved materials including a wide range of inorganic and organic contaminants. Classically defined naphthenic acids (NAs; CnH2n+ZO2) are one of the primary toxic fractions in OSPW and have therefore been the subject of considerable research interest. Most studies employ considerable sample cleanup followed by liquid chromatography and/or high-resolution mass spectrometry (HRMS) for the characterization of these complex mixtures. However, these strategies can be time- and cost-intensive, limiting the scope of research and adoption for regulatory purposes. Condensed phase membrane introduction mass spectrometry (CP-MIMS) is emerging as a “fit-for-purpose” approach for the analysis of NAs. This technique directly interfaces the mass spectrometer with an aqueous sample using a hydrophobic semi-permeable membrane, requiring only pH adjustment to convert NAs to a membrane-permeable form. Here, we examine the perm-selectivity of classical NAs (O2) relative to their more oxidized counterparts (O3–O7) and heteroatomic (N, S) species collectively termed naphthenic acid fraction compounds (NAFCs). The investigation of 14 model compounds revealed that classically defined NAs are greater than 50-fold more membrane permeable than their oxidized/heteroatomic analogs. HRMS analysis of real OSPW extracts with and without membrane clean-up further supported selectivity towards the toxic O2 class of NAs, with >85% of the overall signal intensity attributable to O2 NAs in the membrane permeate despite as little as 34.7 ± 0.6% O2 NAs observed in the directly infused mixture. The information collected with HRMS is leveraged to refine our method for analysis of NAs at unit mass resolution. This new method is applied to 28 archived real-world samples containing NAs/NAFCs from constructed wetlands, OSPW, and environmental monitoring campaigns. Concentrations ranged from 0–25 mg/L O2 NAs and the results measured by CP-MIMS (unit mass) and SPE-HRMS (Orbitrap) showed good agreement (slope = 0.80; R2 = 0.76).

Aqueous naphthenic acids and polycyclic aromatic hydrocarbons in a meso-scale spill tank affected by diluted bitumen analyzed directly by membrane introduction mass spectrometry

With the increasing use of unconventional, heavy crude oils there is growing interest in potential impacts of a diluted bitumen (DB) spill in marine and freshwater environments. DB has the potential to release several toxic, trace organic contaminants to the water column. Here, the aqueous concentrations and compositions of two classes of organic contaminants, naphthenic acids (NAs) and polycyclic aromatic hydrocarbons (PAHs), are followed over 8 weeks after a simulated spill of DB (10 L) into a freshwater mesocosm (1200 L) with river sediment (2.4 kg). These complex samples contain biogenic dissolved organic matter, inorganic ions, petroleum contaminants, suspended sediments, and oil droplets. We report the first use of condensed phase membrane introduction mass spectrometry (CP-MIMS) as a direct sampling platform in a complex multi-phase mesocosm spill tank study to measure trace aqueous phase contaminants with little to no sample preparation (dilution and/or pH adjustment). CP-MIMS provides complementary strengths to conventional analytical approaches (e.g., gas- or liquid chromatography mass spectrometry) by allowing the entire sample series to be screened quickly. Trace NAs are measured as carboxylates ([M-H]-) using electrospray ionization and PAHs are detected as radical cations (M+•) using liquid electron ionization coupled to a triple quadrupole mass spectrometer. The DB-affected mesocosm exhibits NA concentrations from 0.3 to 1.2 mg/L, which rise quickly over the first 2 – 5 days , then decrease slowly over the remainder of the study period. The NA profile (measured as the full scan in negative-electrospray ionization at nominal mass resolution) shifts to lower m/z with weathering, a process followed by principal component analysis of the normalized mass spectra. We couple CP-MIMS with high-resolution mass spectrometry to follow changes in molecular speciation over time, which reveals a concomitant shift from classical ‘O2’ naphthenic acids to more oxidized analogues. Concentrations of PAHs and alkylated analogues (C1 – C4) in the DB-affected water range from 0 to 5 μg/L. Changes in PAH concentrations depend on ring number and degree of alkylation, with small and/or lightly alkylated (C0 – C2) PAH concentrations rising to a maximum in the first 4 – 8 days (100 – 200 h) before slowly decaying over the remainder of the study period. Larger and heavily alkylated (C3 – C4) PAH concentrations generally rise slower, with some species remaining below the detection limit throughout the study period (e.g., C20H12 class including benzo[a]pyrene). In contrast, a control mesocosm (without oil) exhibited NA concentrations below 0.05 mg/L and PAHs were below detection limit. Capitalizing on the rapid analytical workflow of CP-MIMS, we also investigate the impacts of sample filtration at the time of sampling (on NA and PAH data) and sample storage time (on NA data only).

Direct, Isomer-Specific Quantitation of Polycyclic Aromatic Hydrocarbons in Soils Using Membrane Introduction Mass Spectrometry and Chemical Ionization.

Polycyclic aromatic hydrocarbons (PAHs) are routinely screened for in soils, where quantitation of structural isomers is critical due to varying toxicity within PAH isomer classes. While chromatographic methods provide isomer resolution, such strategies are cost and time intensive. To address these challenges, we present condensed phase membrane introduction mass spectrometry using liquid electron ionization/chemical ionization (CP-MIMS-LEI/CI) as a direct mass spectrometry technique that provides rapid, quantitative results for PAH isomer measurements in soil samples. A methanol acceptor phase is flowed through a probe-mounted polydimethylsiloxane hollow fiber membrane directly immersed into a dichloromethane/soil slurry. PAHs and dichloromethane co-permeate the membrane into the acceptor solvent, whereas particulates and charged matrix components remain in the sample. A nanoflow of the membrane permeate is then directly infused into a LEI/CI interfaced triple quadrupole mass spectrometer. Diagnostic PAH adduct ions were formed at either M + 45 ([M + CH2Cl + CH3OH-HCl]+) or M + 47 ([M + CHCl2-HCl]+). This allowed the development of specific MS/MS transitions for individual PAH isomers. These transitions were subsequently used for the direct analyses of PAHs in real soils where CP-MIMS-LEI/CI was shown to be rapid (15 soil samples/h) and sensitive (ng/g level detection limits). CP-MIMS-LEI/CI results compared well to those obtained using GC-MS (average percent difference of -9% across 9 PAHs in 8 soil samples), presenting a compelling argument for direct, quantitative screening of PAHs in soils by CP-MIMS-LEI/CI, particularly given the simple workflow and short analytical duty cycle.

Condensed Phase Membrane Introduction Mass Spectrometry with In Situ Liquid Reagent Chemical Ionization in a Liquid Electron Ionization Source (CP-MIMS-LEI/CI)

Direct mass spectrometry has grown significantly due to wide applicability, relative ease of use, and high sample throughput. However, many current direct mass spectrometry methods are largely based on ambient ionization techniques that can suffer from matrix effects and poor selectivity. A strategy that addresses these shortcomings is condensed phase membrane introduction mass spectrometry-liquid electron ionization utilizing in situ liquid reagent chemical ionization (CP-MIMS-LEI/CI). In CP-MIMS measurements, a semipermeable hollow fiber polydimethylsiloxane membrane probe is directly immersed into a complex sample. Neutral, hydrophobic analytes permeating the membrane are entrained by a continuously flowing liquid acceptor phase (nL/min) to an LEI/CI source, where the liquid is nebulized, followed by analyte vaporization and ionization. This study marks the first intentional exploitation of the liquid CP-MIMS acceptor phase as an in situ means of providing liquid chemical ionization (CI) reagents for improved analyte sensitivity and selectivity (CP-MIMS-LEI/CI). Acetonitrile and diethyl ether were used as a combination acceptor phase/CI proton transfer reagent system for the direct analysis of dialkyl phthalates. Using isotopically labeled reagents, the gas phase ionization mechanism was found to involve reagent autoprotonation, followed by proton transfer to dialkyl phthalates. A demonstration of the applicability of CP-MIMS-LEI/CI for rapid and sensitive screening of bis(2-ethylhexyl) phthalate in house dust samples is presented. The detection limit in house dust (6 mg/kg) is comparable to that obtained by conventional analyses, but without time-consuming sample workup or chromatographic separation steps.

Direct analysis of naphthenic acids in constructed wetland samples by condensed phase membrane introduction mass spectrometry.

The application of direct mass spectrometry techniques to the analysis of complex samples has a number of advantages including reduced sample handling, higher sample throughput, in situ process monitoring, and the potential for adaptation to on-site analysis. We report the application of a semi-permeable capillary hollow fibre membrane probe (immersed directly into an aqueous sample) coupled to a triple quadrupole mass spectrometer by a continuously flowing methanol acceptor phase for the rapid analysis of naphthenic acids with unit mass resolution. The intensity of the naphthenic acid-associated peaks in the mass spectrum are normalized to an internal standard in the acceptor phase for quantitation and the relative abundance of the peaks in the mass spectrum are employed to monitor compositional changes in the naphthenic acid mixture using principle component analysis. We demonstrate the direct analysis of a synthetic oil sands process-affected water for classical naphthenic acids (CnH2n+zO2) as they are attenuated through constructed wetlands containing sedge (Carex aquatilis), cattail (Typha latifolia), or bulrush (Schoenoplectus acutus). Quantitative results for on-line membrane sampling compare favourably to those obtained by solid-phase extraction high-resolution mass spectrometry. Additionally, chemometric analysis of the mass spectra indicates a clear discrimination between naphthenic acid-influenced and natural background waters. Furthermore, the compositional changes within complex naphthenic acid mixtures track closely with the degree of attenuation. Overall, the technique is successful in following changes in both the concentration and composition of naphthenic acids from synthetic oil sands process-affected waters, with the potential for high throughput screening and environmental forensics.

Direct Measurement of Acid Dissociation Constants of Trace Organic Compounds at Nanomolar Levels in Aqueous Solution by Condensed Phase-Membrane Introduction Mass Spectrometry.

We report the use of condensed phase-membrane introduction mass spectrometry as a novel method for the determination of acid dissociation constants for hydrophobic organic acids in aqueous solution at nanomolar concentrations. The technique is based on the pH-dependent permeation of analytes through a semipermeable polydimethylsiloxane membrane probe that is immersed directly in aqueous samples. We describe the method and report the dissociation constant (pKa ) values for compounds of biological and environmental relevance, including contaminants, pharmaceuticals, and naphthenic acids. The approach can be applied to individual compounds, combined suites, and complex mixtures at parts-per-billion levels. We report pKa values for 10 carboxylic acids with precision estimates and relative errors (where reliable literature values are available) of <0.1 log units. We report acidity constants for 2-methyl-3-methoxy-4-phenyl butanoic acid (a biomarker for microcystin algal toxins) and 4-t-butylcyclohexane carboxylic acid (a model naphthenic acid) as 4.28 ± 0.03 and 5.15 ± 0.05, respectively. Furthermore, we employ this approach to measure the effect of both temperature and deuterium oxide (heavy water) on acid dissociation, reporting the enthalpy and entropy changes for the ionization of a representative carboxylic acid and substituted phenol. Environ Toxicol Chem 2019;38:1879-1889. © 2019 SETAC.

Mass Spectrometry Based Approach for Organic Synthesis Monitoring.

Current mass spectrometry-based methodologies for synthetic organic reaction monitoring largely use electrospray ionization (ESI), or other related atmospheric pressure ionization-based approaches. Monitoring of complex, heterogeneous systems may be problematic because of sampling hardware limitations, and many relevant analytes (neutrals) exhibit poor ESI performance. An alternative monitoring strategy addressing this significant impasse is condensed phase membrane introduction mass spectrometry using liquid electron ionization (CP-MIMS-LEI). In CP-MIMS, a semipermeable silicone membrane selects hydrophobic neutral analytes, rejecting particulates and charged chemical components. Analytes partition through the membrane, and are then transported to the LEI interface for sequential nebulization, vaporization, and ionization. CP-MIMS and LEI are both ideal for continuous monitoring applications of hydrophobic neutral molecules. We demonstrate quantitative reaction monitoring of harsh, complex reaction mixtures (alkaline, acidic, heterogeneous) in protic and aprotic organic solvents. Also presented are solvent-membrane compatibility investigations and, in situ quantitative monitoring of catalytic oxidation and alkylation reactions.

Direct Analysis of Polyaromatic Hydrocarbons in Soil and Aqueous Samples Using Condensed Phase Membrane Introduction Tandem Mass Spectrometry with Low-Energy Liquid Electron Ionization.

Polyaromatic hydrocarbons (PAHs) are listed as priority pollutants by the United States Environmental Protection Agency (U.S. EPA). PAH-contaminated samples often require extensive sample cleanup before analysis, with the method used dependent upon the sample matrix. We present condensed phase membrane introduction mass spectrometry with liquid electron ionization (CP-MIMS-LEI) as a sensitive and universal technique that can directly analyze both aqueous and soil samples for PAHs without the need for sample clean up or instrumental modifications for different matrixes. The method uses a semipermeable hollow fiber membrane immersion probe to transfer analytes from complex samples into a solvent acceptor phase that is directly entrained at nanoliter/min flows to an LEI-interfaced mass spectrometer. The resulting aerosol is desolvated under vacuum leading to analyte vaporization and subsequent electron ionization. Electron energy and LEI vaporization capillary position were examined and optimized for PAHs. The CP-MIMS probe was directly immersed in complex aqueous matrixes, demonstrating low nanogram per liter PAH detection limits and response times of ≤1.6 min. For soil sample analysis, 2-propanol was found to be the optimal PAH sampling solvent. Soil samples were briefly sonicated in 2-propanol, followed by direct CP-MIMS measurement. Soil sample throughput was ca. 15 samples/h, with PAH quantitation successful at microgram per kilogram levels. The workflow is remarkably simple, fast, green, and leads to reproducible results that enable high-throughput screening of heterogeneous soil samples.

Direct quantitation and characterization of fatty acids in salmon tissue by condensed phase membrane introduction mass spectrometry (CP-MIMS) using a modified donor phase.

Existing mass spectrometric methods for the analysis of fatty acids often require derivatization, chromatographic separations, and/or extensive sample preparation. Direct mass spectrometry strategies can avoid these requirements, but may also suffer from poor quantitation and/or lack of sensitivity. Condensed phase-membrane introduction mass spectrometry (CP-MIMS) provides direct quantitative measurements of analytes in complex samples with little or no sample preparation. CP-MIMS uses a semipermeable membrane to transfer neutral, hydrophobic compounds from real-world samples to a mass spectrometer. The results presented utilize aqueous/organic sample solvent (donor) mixtures to allow for the sensitive (pptr) detection of a range of fatty acids. The relative sensitivity across a homologous series of fatty acids is observed to change, favoring short- or long-chain fatty acids, depending on the amount of miscible co-solvent added to the donor phase. Further, lithium acetate added online via the acceptor phase was used in tandem mass spectrometry experiments to determine the location of double bonds in polyunsaturated fatty acids (PUFAs). The method was applied to direct measurements and structural determinations for selected PUFAs in salmon tissue samples. Standard addition was employed to quantify the amount of PUFAs in a variety of salmon samples, yielding 0.27-0.42 and 0.40-0.84 w/w % for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively, for Sockeye and Chinook salmon, in good agreement with the literature. This work presents, to our knowledge, the first use of CP-MIMS for the direct analysis of fatty acids in oily foodstuff samples. Graphical abstract ᅟ.

Polymer Inclusion Membranes with Condensed Phase Membrane Introduction Mass Spectrometry (CP-MIMS): Improved Analytical Response Time and Sensitivity.

Condensed phase membrane introduction mass spectrometry (CP-MIMS) is an online, in situ analysis technique for low volatility analytes. Analytes diffuse through a hollow fiber membrane, where they are then dissolved by a liquid (condensed) acceptor phase flowing through the membrane lumen. Permeating analytes are entrained to an atmospheric pressure ionization source for subsequent measurement by a mass spectrometer. Larger analytes, with inherently lower diffusivities, suffer from lengthy response times and lower sensitivity, limiting the use of CP-MIMS for their online, real-time measurement. We present the use of a heptane cosolvent in a methanol acceptor phase in combination with a polydimethylsiloxane (PDMS) membrane. The heptane generates an in situ polymer inclusion membrane (PIM) with the PDMS. We report improved measurement response times and greater sensitivity across a suite of analytes studied (gemfibrozil, nonylphenol, triclosan, 2,4,6-trichlorophenol, and naphthenic acids), with detection limits in the low parts per trillion (ppt) range. These improvements are attributed to increasing analyte diffusivities, as well as increased analyte partitioning across the PIM. Response times are ∼3× faster for the larger analytes studied, and calibration sensitivity is improved by up to ∼3.5× using 0.046 mole fraction heptane in the methanol acceptor. We report the use of short sample exposure times and the use of non-steady-state signals to reduce the analytical duty cycle, and illustrate that the use of a PIM provides a simple and robust variant of CP-MIMS amenable to rapid screening of analytes in complex samples.

Rapid Screening of Carboxylic Acids from Waste and Surface Waters by ESI-MS/MS Using Barium Ion Chemistry and On-Line Membrane Sampling.

Negative ion tandem mass spectrometric analysis of aliphatic carboxylic acids often yields only non-diagnostic ([M - H](-)) ions with limited selective fragmentation. However, carboxylates cationized with Ba(2+) have demonstrated efficient dissociation in positive ion mode, providing structurally diagnostic product ions. We report the application of barium adducts followed by collision induced dissociation (CID), to improve selectivity for rapid screening of carboxylic acids in complex aqueous samples. The quantitative MS/MS method presented utilizes common product ions of [M - H + Ba](+) precursor ions. The mechanism of product ion formation is investigated using isotopically labeled standards and a series of structurally related carboxylic acids. The results suggest that hydrogen atoms in the β and γ positions yield common product ions ([BaH](+) and [BaOH](+)). Furthermore, the diagnostic product ion at m/z 196 serves as a qualifying ion for carboxylate species. This methodology has been successfully used in conjunction with condensed phase membrane introduction mass spectrometry (CP-MIMS), with barium acetate added directly to the methanol acceptor phase. The combination enables rapid screening of carboxylic acids directly from acidified water samples (wastewater effluent, spiked natural waters) using a capillary hollow fiber PDMS membrane immersion probe. We have applied this technique for the direct analysis of complex naphthenic acid mixtures spiked into natural surface waters using CP-MIMS. Selectivity at the ionization and tandem mass spectrometry level eliminate isobaric interferences from hydroxylated species present within the samples, which have been observed in negative electrospray ionization.

A semi-quantitative approach for the rapid screening and mass profiling of naphthenic acids directly in contaminated aqueous samples.

We report the use of a direct sampling, online analytical approach for the determination of acid extractable naphthenic acids in complex aqueous samples, known as condensed phase membrane introduction mass spectrometry (CP-MIMS). The technique employs a capillary hollow fibre semi-permeable membrane probe configured for immersion into a pH adjusted sample. A continuously flowing methanol acceptor phase transfers naphthenic acids to an electrospray ionization source, operated in negative ion mode, whereupon they are analysed by mass spectrometry as [M-H](-) ions. High-resolution mass spectrometry is used to characterize the influence of sample pH on membrane transport of multiple components of complex naphthenic acid mixtures. We demonstrate the use of CP-MIMS for semi-quantitative analysis of real-world samples using selected ion monitoring and full scan mass spectra at unit mass resolution. The technique has also been employed to continuously monitor the temporal evolution in the mass profile and concentrations of individual naphthenic acid isomer classes in heterogeneous solutions during adsorption processes. Copyright © 2015 John Wiley & Sons, Ltd.

Condensed Phase Membrane Introduction Mass Spectrometry with Direct Electron Ionization: On-line Measurement of PAHs in Complex Aqueous Samples.

Polycyclic aromatic hydrocarbons (PAHs) are USEPA regulated priority pollutants. Their low aqueous solubility requires very sensitive analytical methods for their detection, typically involving preconcentration steps. Presented is the first demonstrated ‘proof of concept’ use of condensed phase membrane introduction mass spectrometry (CP-MIMS) coupled with direct liquid electron ionization (DEI) for the direct, on-line measurement of PAHs in aqueous samples. DEI is very well suited for the ionization of PAHs and other nonpolar compounds, and is not significantly influenced by the co-elution of matrix components. Linear calibration data for low ppb levels of aqueous naphthalene, anthracene, and pyrene is demonstrated, with measured detection limits of 4 ppb. Analytical response times (t10%–90% signal rise) ranged from 2.8 min for naphthalene to 4.7 min for pyrene. Both intra- and interday reproducibility has been assessed (<3% and 5% RSD, respectively). Direct measurements of ppb level PAHs spiked in a variety of real, complex environmental sample matrices is examined, including natural waters, sea waters, and a hydrocarbon extraction production waste water sample. For these spiked, complex samples, direct PAH measurement by CP-MIMS-DEI yielded minimal signal suppression from sample matrix effects (81%–104%). We demonstrate the use of this analytical approach to directly monitor real-time changes in aqueous PAH concentrations with potential applications for continuous on-line monitoring strategies and binding/adsorption studies in heterogeneous samples.

Ionization suppression effects with condensed phase membrane introduction mass spectrometry: methods to increase the linear dynamic range and sensitivity.

Condensed phase membrane introduction mass spectrometry (CP-MIMS) is an online analytical method that allows for the direct, trace level measurement of a wide range of analytes in complex samples. The technique employs a semi-permeable membrane that transfers analytes from a sample into a flowing acceptor solvent, which is directly infused to an atmospheric pressure ionization source, such as electrospray or atmospheric pressure chemical ionization. While CP-MIMS and variants of the technique have been in the literature for nearly a decade, much of the work has focused on instrument development. Few studies have thoroughly addressed quantitative methods related to detection limits, ionization suppression, or linear dynamic range. We examine ionization suppression in the direct rapid quantitation of analytes by CP-MIMS and introduce several analytical strategies to mitigate these effects, including the novel implementation of a continuously infused internal standard in the acceptor phase solvent, and modulation of acceptor phase flow rate. Several representative analytes were used to evaluate this approach with spiked, complex sample matrices, including primary wastewater effluent and artificial urine. Also reported are improved measured detection limits in the low part-per-trillion range, using a 'stopped-flow' acceptor mode.

Delicate polydimethylsiloxane hollow fibre membrane interfaces for condensed phase membrane introduction mass spectrometry (CP‐MIMS)

On-line analytical techniques such as condensed phase membrane introduction mass spectrometry (CP-MIMS) permit direct and rapid analyte measurements in complex samples. Direct, rapid analytical methods are desirable because they eliminate potential contamination and/or dilution from sample workup steps, facilitate rapid sample screening and allow 'real-time' monitoring applications. PDMS hollow fibre membrane (HFM) flow cell interfaces (215 µm, 35 µm, and 0.5 µm thick composite) were coupled with an electrospray ionization (ESI) triple quadrupole mass spectrometer. A simultaneous push/pull methanol acceptor phase delivery system and membrane mounting via epoxy potting ensured that the delicate membranes were not ruptured during construction or sample measurements. Both flow cell and direct insertion 'J-Probe' interfaces using the 0.5 µm thick composite PDMS HFM were utilized for direct naphthenic acid measurements. Delicate HFM CP-MIMS interfaces were used for the rapid screening and continuous, on-line monitoring of carboxylic acids and hydroxylated compounds directly in complex sample matrices under ambient conditions at pptr - ppb detection limits. Push/pull acceptor phase (methanol) delivery maintained ambient hydrostatic pressures within the HFMs, improving ESI stability and analytical sensitivity, especially with stopped acceptor flow operation. Signal response times less than 2 min were achieved for thin, composite PDMS HFMs at 30°C. The continuous monitoring of naphthenic acid degradation was demonstrated. Delicate PDMS HFM CP-MIMS interfaces were developed and used for the direct, on-line detection of low volatility, polar analytes in complex aqueous samples. Composite PDMS HFM interfaces yielded the best overall analytical performance improvements, and were used to demonstrate the direct measurement of naphthenic acids in complex aqueous samples.