Ion-Molecule Reactions for the Differentiation of Primary, Secondary and Tertiary Hydroxyl Functionalities in Protonated Analytes in a Tandem Mass Spectrometer

A mass spectrometric method utilizing gas-phase ion-molecule reactions of 1-butanethiol and di-tert-butyl peroxide has been developed for the differentiation of primary, secondary and tertiary hydroxyl functionalities in protonated analytes in a FT-ICR mass spectrometer

Data-Dependent Neutral Gain MS3: Toward Automated Identification of the N-Oxide Functional Group in Drug Metabolites

We report here an automated method for the identification of N-oxide functional groups in drug metabolites by using the combination of liquid chromatography/tandem mass spectrometry (LC/MSn) based on ion-molecule reactions and collision-activated dissociation (CAD). Data-dependent acquisition, which has been readily utilized for metabolite characterization using CAD-based methods, is adapted for use with ion-molecule reaction-based tandem mass spectrometry by careful choice of select experimental parameters. Two different experiments utilizing ion-molecule reactions are demonstrated, data-dependent neutral gain MS3 and data-dependent neutral gain pseudo-MS3, both of which generate functional group selective mass spectral data in a single experiment and facilitate increased throughput in structural elucidation of unknown mixture components. Initial results have been generated by using an LC/MSn method based on ion-molecule reactions developed earlier for the identification of the N-oxide functional group in pharmaceutical samples, a notoriously difficult functional group to identify via CAD alone. Since commercial software and straightforward, external instrument modification are used, these experiments are readily adaptable to the industrial pharmaceutical laboratory