Differential mobility spectrometry combined with multiple ion monitoring for bioanalysis of disulfide-bonded peptides with inefficient collision-induced dissociation fragmentation.

Abstract

It is challenging to develop a multiple reaction monitoring (MRM) method for some disulfide-bonded peptides with inefficient collision-induced dissociation fragmentation. This study describes a new methodology using differential mobility spectrometry (DMS) combined with multiple ion monitoring (MIM) to enhance bioanalytical sensitivity for sunflower trypsin inhibitor. By combining DMS with MIM to monitor the intact precursor ion in Q1 and Q3 MS analyzers, a lower limit of quantitation at 0.125 ng/ml was achieved to quantify sunflower trypsin inhibitor in rat plasma, representing a 40-fold sensitivity improvement over MIM without DMS. DMS coupled with MIM method provides triple quadrupole MS users an effective means to overcome challenges in analyzing disulfide-bonded peptides or other analytes that do not have useful collision-induced dissociation fragment ions for MRM analysis.