Next Generation Elemental Mass Spectrometry of Nonmetals

Georgetown University, Washington DC

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Abstract

Project Summary The goal of this project is to improve the robustness and sensitivity of a novel elemental mass spectrometry (MS) technology, enabling rapid absolute quantitation of biomolecules without compound- specific standards. Absolute quantitation of small and large molecules is imperative for assessing their biological roles and effects. For example, xenobiotics, such as pharmaceuticals and environmental contaminants as well as their biotransformation products, need to be quantified to characterize toxicity. LC-MS methods are widely used for detecting and identifying compounds in a nontargeted fashion but these techniques require an individual standard per compound, presenting difficulties when standards are not available. To alleviate this limitation, we have developed a new LC-elemental MS technology for high-sensitivity quantitation of compounds without analyte-specific standards via tracing F, Cl, S, and P atoms intrinsic to the chemical structures of the compounds. Unlike conventional elemental MS techniques that form ions inside a hot plasma, the new approach utilizes the plasma as a reactor to create stable neutral species from elements, e.g. HF, HCl, H2SO4, and H3PO3 which are then ionized by ion-neutral reactions in post-plasma area. This approach has opened new frontiers in elemental MS capabilities such as high-resolution detection and ion mobility separations for enhanced analytical performance. In this project, we will improve the detection sensitivity and will enhance matrix tolerance of this new technology for facile and accurate quantitation in complex matrices. The improvements will originate from three aspects: 1) increasing selectivity of ionization reactions for each plasma-generated element-specific neutral species, 2) tuning plasma chemistry for enhanced generation of element- specific neutrals, and 3) increasing the efficiency of neutral transfer to ionization area via improved designs of the post-plasma chemical ionization interface. Further we will demonstrate the analytical capabilities of the enhanced technology in characterization of small and large molecules by developing methods to quantify both stable and protein-bound reactive drug metabolites.