October 2009 Meeting Announcement, Delaware Valley Mass Spectrometry Discussion Group

• Topic: "Applications of Orbitrap MS in Drug Discovery and Development "

• Speaker: John Erve, Wyeth

• Date: Monday, October 12, 2009. 6:30 PM

• Time: Social Hour: 6:30 PM.
  Talk: 7:30 PM.
  Please RSVP to John Erve ERVEJ@wyeth.com by Thursday October 8th.

• Place: Department of Chemistry, Villanova University (Room 102, Mendel Hall)

• Directions:

• Abstract: The LTQ/Orbitrap is a mass spectrometer with high mass accuracy and resolving powers of up to 100 K (at 400 m/z). Due to scan speed limitations, however, the use of the highest resolving power available can be problematic when conducting LC/MS experiments. This limitation can be overcome when combing the LTQ/Orbitrap with a Triversa Nanomate. When using an ESI-chip with the Nanomate in direct infusion mode, the nanospray process allows very long analysis times thereby removing any scan time limitations with respect to resolving power. In this seminar, applications of the LTQ/Orbitrap together with the Nanomate will be described in which direct infusion of samples following ZipTip clean-up at 100 K resolving power allows metabolites to be identified by sub parts-per-million mass accuracies. These include, metabolite profiling from a rat metabolism study of prazosin and metabolite profiling of rat brain microdialysates samples of several CNS drugs. In addition, the concept of spectral accuracy will be described together with spectral accuracy characteristics of ten high molecular weight compounds acquired on the LTQ/Orbitrap at different resolving power settings and its application to elemental composition determination.

• Bio: John is a native of Chicago, Illinois and he received his BS and MS degrees in Chemistry at the University of Chicago in 1986 and 1987, respectively. After graduation, he worked at the University of Chicago Hospitals in the Department of Nutrition performing trace metal analysis using ICP/MS. John began graduate studies at Oregon State University in 1991 and earned his PhD in Toxicology under Donald J. Reed in 1995 with a thesis on protein modifications due to xenobiotics. An NIEHS postdoctoral training grant allowed John to continue basic research in the area of protein modifications and mass spectrometry at Vanderbilt (Nashville, Tennessee) in the Center for Molecular Toxicology. In January 2000 he joined Gentest (now BD-Biosciences, Woburn, Massachusetts) as a Study Director for contract research in support of drug discovery programs. In June of 2002, he joined AstraZeneca (Södertälje, Sweden) where he was involved in characterizing reactive metabolites and their protein adducts in an effort to better understand the role of reactive intermediates in causing drug toxicity. Since August of 2004 he is a Principal Scientist at Wyeth (Collegeville, Pennsylvania) responsible for metabolite identification in drug development projects. His research interests are mechanistic toxicology and the use of biological mass spectrometry to characterize protein modifications and metabolic pathways of toxicological significance.

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