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

Abstract

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 fibre 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 work up or chromatographic separation steps.

Direct mass spectrometric analysis of naphthenic acids and polycyclic aromatic hydrocarbons in waters impacted by diluted bitumen and conventional crude oil

“…To enhance sensitivity, CP-MIMS-LEI measurements were performed in stopped-flow mode (Duncan et al, 2011;Krogh and Gill, 2018;Vandergrift et al, 2020). To do so, a 6-port valve system was included directly upstream from the passive flow splitter.…”

“…The membrane rejects ionized matrix components and particulate matter while allowing hydrophobic analytes to permeate through and dissolve into a flowing acceptor phase solvent (Krogh and Gill, 2018). The acceptor phase (typically methanol), containing the membrane-permeable fraction of the sample, is then infused into an appropriate ionization source, often electrospray or liquid electron ionization (Termopoli et al, 2019a;Vandergrift et al, 2020), to provide real-time results, which can be employed to provide both qualitative and quantitative data. This method has been applied to a wide range of analytes and sample matrices, including pharmaceuticals in wastewater (Duncan et al, 2016b), fatty acids in salmon tissue (Borden et al, 2019), NAs in water (Duncan et al, 2016a) and constructed wetlands (Duncan et al, 2020), PAHs in water and soil samples (Termopoli et al, 2016;Vandergrift et al, 2019), and the determination of acid dissociation constants of trace organic contaminants in aqueous solutions (Feehan et al, 2019).…”

Analysis of impurities in pharmaceuticals by LC‐MS with cold electron ionization

“…17,18 Cappiello and coworkers presented several generations and versions of this type of instrument and utilized it in a range of applications. [19][20][21][22][23][24] This technology was also used by Gill and coworkers. 24 Recently, Mondello and coworkers also had begun working on EI-LC-MS applications.…”

“…[19][20][21][22][23][24] This technology was also used by Gill and coworkers. 24 Recently, Mondello and coworkers also had begun working on EI-LC-MS applications. [25][26][27] All of the latter use standard EI ion source of commercial MS systems, with a prior desolvation chamber in the current version of Mondello and coworkers, 18 and base the interface on thermospray formation with low liquid flow rates of the order of 1 μl/min that are allowed to enter the ion source.…”

“…Later, the idea of EI‐LC‐MS was developed by several groups 17,18 . Cappiello and coworkers presented several generations and versions of this type of instrument and utilized it in a range of applications 19–24 . This technology was also used by Gill and coworkers 24 .…”