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.