A Passive Membrane System for On‐line Mass Spectrometry Reagent Addition

Rationale

Post-separation addition of chemical modifiers in liquid chromatography-mass spectrometry (LC-MS) is widely used for improving ionization sensitivity and selectivity. This is typically accomplished using a post column T-junction, which can result in sample dilution and imperfect mixing. We present a passive semi-permeable hollow fibre membrane approach for the addition of chemical modifiers that avoids these issues.

Methods

Model compounds were directly infused by flow injection to an electrospray ionization triple quadrupole mass spectrometer after passing through a polydimethylsiloxane hollow fibre membrane. Ionization enhancement reagents were introduced into the flowing stream by membrane permeation from aqueous solutions. Ionization enhancement from volatile acids and bases in positive and negative electrospray ionization was evaluated to assess feasibility for this approach.

Results

The membrane-based apparatus resulted in relative ionization enhancement factors of up to 14×, depending upon the analyte, reagent, and ionization mode used. Ionization enhancement signal stability is reasonable (RSD 5-7 %) for extended periods from the same reagent solution, and minimal analyte dilution is observed. A proof-of-concept demonstration of the chromatographic ‘trifluoroacetic acid fix’ strategy is presented.

Conclusions

An on-line mass spectrometry ionization reagent addition method with potential post-chromatography reagent addition applications was developed using a hollow fibre polydimethylsiloxane membrane. This approach offers a promising alternative to traditional methods requiring additional hardware such as pumps and T-junctions that can result in sample dilution and imperfect reagent mixing.