Chicago Mass Spectrometry Discussion Group December 2015 Meeting 

Please join us at Northwestern University's Pancoe Auditorium in Evanston on Tuesday, December 8th, 2015 for a lecture by Prof. Hilkka I. Kenttämma from Purdue University's Department of Chemistry. Dinner will be at 6:30 with the lecture at 7:00 pm

Title: New Approaches for Structural Characterization of Unknown Organic Compounds by Tandem Mass Spectrometry

Abstract: Adverse drug reactions are believed to be a leading cause of morbidity and mortality in United States healthcare and markedly increase the cost of drug development. Pharmacologically active or toxic drug metabolites and impurities are frequently implicated as potential sources of serious adverse drug reactions. This is one of the major reasons for new drug candidates being withdrawn from the market. The most challenging task in addressing this issue is the rapid detection and structural elucidation of trace levels of unknown drug metabolites and impurities. However, all common analytical methods developed for this task, including nuclear magnetic resonance spectroscopy, gas chromatography, capillary electrophoresis, liquid chromatography, mass spectrometry and tandem mass spectrometry, have serious limitations. Furthermore, only the methods based on tandem mass spectrometry enable the unambiguous identification of organic compounds directly in complex mixtures. While MS2 using collision-activated dissociation (CAD) has been highly successful in identification of known compounds in complex mixtures, this approach often does not allow the unambiguous identification of previously unknown compounds as ionized isomeric compounds often fragment in a similar manner. We are in the process of developing fast, automated methodology based on multi-stage tandem mass spectrometry utilizing functional-group selective bimolecular reactions (instead of CAD) that enables unambiguous structural characterization of previously unknown drug metabolites and impurities in complex mixtures. This involves the development of a library of reagents that can be used to reliably and predictably identify functional groups in previously unknown, protonated polyfunctional analytes, methods for the fast introduction of several reagents into a mass spectrometer to probe for the presence of several functionalities in (protonated) analytes as they elute from HPLC, and automation of the experiment.

About the Speaker:  In the Kenttämma lab, mechanistic, kinetic and thermochemical studies are carried out on reaction intermediates that are important for example in organic and inorganic synthesis, carcinogenesis, and the action of antitumor drugs; e.g., radical cations, radicals, borocations, carbene ions, and phosphorus cations. Theoretical methods are used to complement experiments carried out using Fourier-transform ion cyclotron resonance and linear quadrapole ion trap mass spectrometry. New strategies are developed for the synthesis and study of interesting ions inside the mass spectrometer. Multiple-stage tandem mass spectrometry experiments are being developed for selective ionization and structural characterization of polyfunctional organic compounds, including amino acids, peptides, oligosaccharides, and degraded lignin. The possibility to use functional group selective ion-molecule reactions in mass spectrometric analysis of organic compounds is being explored.

Lab site: https://www.chem.purdue.edu/hilkka/

Chicago Mass Spectrometry Discussion Group
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