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

Abstract

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.

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

“…While this pH effect is readily observed for both CC-and DBcontaminated samples (Figure 2), it is more pronounced in the latter due to the higher concentration of NAs in the DB source oil. We have previously reported pKa values for NA isomer classes to be in the range of 5.1-5.7 (Feehan et al, 2019). Such values are anticipated to result in a levelling of aqueous NA concentrations at pH > 8, depending on the value of pPwo, which varies across isomer classes (Bertheussen et al, 2018b).…”

“…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). Herein, we determine aqueous-phase concentrations of NA and PAH contaminants in constructed water samples containing DB and CC oil over a range of salinity and pH.…”

Retention mechanism of pH‐peak‐focusing in countercurrent chromatographic separation of baicalin and wogonoside from Scutellaria baicalensis Georgi

“…The mixture was kept at 25°C for 72 h. Finally, the concentration of baicalin in the aqueous solution both inside and outside the bag was determined [36]. Provided that the pH of the solution is known (or can be determined), the p K a can be calculated using a variant of the familiar Henderson–Hasselbalch equation [37] as follows: The p K a value of baicalin could then be calculated by the equation: where pH 1 is the pH of the buffer solution outside the bag, pH 2 is the pH of the buffer solution inside the bag, and R is the concentration ratio of baicalin in the internal versus external buffer solution, respectively.…”

Membrane Sampling Separates Naphthenic Acids from Biogenic Dissolved Organic Matter for Direct Analysis by Mass Spectrometry

“…Condensed phase membrane introduction mass spectrometry (CP-MIMS) has been demonstrated as an analytical method capable of rapidly screening NAs directly in water samples, with very little or no sample preparation. ,− In CP-MIMS, a capillary hollow fiber poly­(dimethylsiloxane) (PDMS) polymer membrane is mounted on an immersion probe and connected to a flowing acceptor phase solvent. After sample acidification, protonated NAs partition into and diffuse through the PDMS into the acceptor solvent for subsequent, direct infusion and ionization in an atmospheric pressure ion source of a mass spectrometer.…”