Application and Development of Multidimensional Mass Spectrometry-Based Methods for the Analysis of Pharmaceuticals and Metabolites in Biological Samples

Abstract

New hybrid mass spectrometry devices are essential for bioanalytical method development and applications. Data independent workflow and SWATH enabled the developed QUAL/QUANT dual derivatization methods to analyze polar metabolites in urine samples. While collision-induced dissociation (CID) of metal adducts (Na or K) is challenging, electron-induced dissociation (EID) of adducts is generating similar fragments to that observed in electron impact ionization. Differential ion mobility spectrometry (DMS) with modifier is a powerful method to optimize isomeric analytes' separation (resolution, peak capacity, and sensitivity). Computational model using molecular mechanics and density functional theory (DFT) allowed characterizing modifiers cluster formation. Modifier mixtures were found to have significant effects on DMS sensitivity, selectivity, and peak capacity, which opens new possibilities for optimizing DMS separation and the analysis of complex biological samples.