Infrared isomer-specific fragmentation for the identification of aminobutyric acid isomers separated by differential mobility spectrometry

Abstract Metabolomics strongly relies on liquid chromatography hyphenated to tandem mass spectrometry (LC-MS/MS) for the separation and identification of metabolites. Retention times and fragmentation mass spectra are used as identification parameters. A complementary approach is proposed here based on alternative approaches for both the separation and identification, and is illustrated in the case of isomeric forms of aminobutyric acids (C4H9NO2). Differential mobility spectrometry (DMS), a very efficient method for the separation of isomers of small molecules, is coupled with high resolution tandem mass spectrometry Fourier transform ion cyclotron resonance (FT-ICR). Identification of the DMS peaks associated with the various isomers is based on isomer-specific infrared multiple photon dissociation (IRMPD) in the mid-infrared range. Two operation modes of the DMS-MS/MS(IRMPD) are used. Structural identification of the various isomers is first achieved based on the comparison of IRMPD spectra of DMS- and mass-selected ions with IR absorption spectra of candidate structures derived from quantum chemical calculations. For this purpose, the DMS device is used in selective mode. Alternatively, when the DMS is using in scanning mode, identification can also be achieved based on specific depletion of DMS peaks at selected IR wavelength. These two operation modes for identification of isomers are illustrated in conjunction with the use of modifier-assisted DMS separation.