Speaker
Description
Common amino acids (AA) and their catabolic derivatives have been shown to constitute a class of biomarkers for early diagnosis of diseases such as cancers. In the frame of metabolomics techniques based on tandem mass spectrometry, different strategies can be employed for the separation step, in order to minimize the chemical noise and contribute to the resolution of isobaric or isomeric species. In this context, ion mobility spectrometry represents an interesting alternative, or complementary approach, to condensed phase chromatography which require pre- or post-column derivatization.
We propose here to investigate the performance of differential ion mobility spectrometry (DIMS) coupled to tandem mass-spectrometry for the separation of the 20 common AA. With the exception of Leucine/Isoleucine, all pairs of AA can be separated using N$_2$ as a carrier gas. Peak-to-peak resolution for each pairwise combination of AA ions are systematically derived for electric field strength values, and it turns out that ~80% can be baseline separated.
The potential of the DIMS-MS/MS experiment in combination to infrared activation is also presented for the separation and identification of sarcosine, a biomarker candidate of prostate cancer, from isomers. Baseline separation of protonated sarcosine from alpha- and beta-alanine isomers can be easily achieved using only N$_2$ as carrier gas. Identification of DIMS peak is performed using an isomer specific activation mode, where DIMS- and mass-selected ions are irradiated at selected wavenumbers allowing for the specific fragmentation through an infrared multiple photon dissociation (IRMPD) process. Based on the comparison of IR spectra of the three isomers, we show that specific depletion of the two protonated alpha- and beta-alanine can be achieved, thus allowing for clear identification of the sarcosine peak. It is also demonstrated that DIMS-MS/MS(IRMPD) spectra in the carboxylic C=O stretching region allows for the resolution of overlapping peaks.
