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.