E19-01: LC/MS: Theory, Instruments and Applications

Two-Day Course 
Sunday, Nov. 17 – Monday, Nov. 18; 8:30am – 5:00pm
Dr. Guodong Chen, Bristol-Myers Squibb, Princeton, NJ 
Dr. Ragu Ramanathan, Pfizer, Groton, CT 

This two-day course is designed to be an introduction to the theory and practical implementation of LC/MS and LC/MS/MS technology in the laboratory. It emphasizes problem-solving skills with examples encountered in industrial and academic research including characterization of trace level drug substance impurities and degradation products, identification of drug metabolites, and the analysis of natural products and bio-molecules. The interpretation of mass spectra will be illustrated with practical examples. In addition, structure determination of proteins and peptides will be presented, including antibody-drug conjugates. This course will focus on atmospheric pressure ionization interfaces including electrospray and atmospheric pressure chemical ionization, and will survey the various mass analyzer options. This course will address issues regarding the coupling of capillary HPLC, microbore HPLC, UHPLC and standard 4.6 mm chromatography. A thorough coverage of approaches toward method development for both qualitative and quantitative analysis of pharmaceutical products and biomolecules will provide a
good starting point for understanding the practical issues facing implementation of LC/MS in the
laboratory. Furthermore, an overview of the current state-of-the-art of automating the LC/MS laboratory including the interfacing of automated sample preparation devices will be provided. Finally, this course will cover analytical method development in protein mass spectrometry combined with separation techniques for analyzing proteins and peptides.

This two-day course is designed for practicing LC/MS chemists (new users, chromatographers, analytical chemists, protein chemists, and laboratory managers)

1. Introductions to Liquid Chromatography (LC) / Mass Spectrometry (MS)
     a. History
     b. Ionization
     c. Atmospheric pressure ionization API (ESI, APCI)
2. Mass Analyzers
     a. Quadrupoles
     b. Ion trap
     c. Time-of-flight
d. Orbitrap
     e. Tandem mass spectrometry (MS/MS)  
3. LC/MS Method Development
     a. Issues:  sample preparation
     b. LC/MS Interface
4. Automation and High-Throughput Sample Analysis
5. Application in Drug Metabolism
6. Applications—Small Molecules, Pharmaceuticals, Natural Products
     a. Structure Elucidation, Identification and Quantitation
7. Applications—Proteins and Peptides
     a. Protein/peptide characterization and structural problems
     b. Antibody-drug conjugates
     c. Quantitative Analysis

Dr. Guodong Chen (Course Director) has extensive pharmaceutical research experience in major pharmaceutical companies, including Eli Lilly and Company, Schering-Plough and Bristol-Myers Squibb. Currently, he heads analytical/mass spectrometry group at Bristol-Myers Squibb’s Princeton site, providing analytical/mass spectrometric support to drug discovery programs and development projects in small molecule pharmaceuticals and biologics. His matrix team leadership includes Program Leader. His research interests include development and application of advanced analytical/mass spectrometry techniques in pharmaceutical research and development. He has over 85 research publications in peer-reviewed journals and book chapters in pharmaceutical analysis, multiple patents on antibody therapeutics and three edited/co-edited books, “Characterization of Impurities and Degradants Using Mass Spectrometry” (Wiley), “Protein and Peptide Mass Spectrometry in Drug Discovery” (Wiley) and “Characterization of Protein Therapeutics Using Mass Spectrometry” (Springer). He serves on the Editorial Board for Journal of the American Society for Mass Spectrometry. His scientific contributions include short course instructor at EAS, Pittcon and ASMS conferences, invited speaker at national/international conferences and academic institutes with over 100 presentations, and reviewer for International Journal of Mass Spectrometry, Journal of Mass Spectrometry, Journal of the American Society for Mass Spectrometry, Rapid Communication in Mass Spectrometry, Journal of Proteomics & Bioinformatics, Journal of Proteome Research, Expert Review of Proteomics, Organic Process Research & Development, Journal of Pharmaceutical Sciences, Analytical Chemistry, Analytical Biochemistry, Journal of Pharmaceutical and Biomedical Analysis, Drug Discovery Today, mAbs, Chemistry Today, AAPS PharmSciTech and Wiley/Springer book proposals. He also organized/chaired scientific sessions at various forums, including EAS, CPSA, Pittcon, ACS, ASMS and HOS conferences. Dr. Chen was the Chairperson of the North Jersey Section of ACS Mass Spectrometry Discussion Group (2004). He was an invited Analytical Chemistry Program Chair for ACS MARM Conference (2005) and President of Chinese American Chemical Society-Tri State (2007). He served as the founding Chairperson of the ASMS Biotherapeutics Interest Group (2009-2011). He was an invited organizer and Program Chair for 28th ASMS Sanibel Conference (2016). He received his Ph.D. in Analytical Chemistry from Purdue University under the direction of Professor R. Graham Cooks.

Dr. Ragu Ramanathan received his B.S. degree in Chemistry from the University of Southern Mississippi in 1988 and a Ph.D. degree in Analytical/Physical Chemistry from the University of Florida in 1994. From 1995-1997, Dr. Ramanathan was a postdoctoral researcher at the Washington University (St. Louis, MO) NIH mass spectrometry resources, where he applied mass spectrometry to cancer research and protein characterization.  Over the years, Dr. Ramanathan has applied his expertise in mass spectrometry, analytical chemistry, drug metabolism and pharmacokinetics to discover and develop drugs at several pharmaceutical research and contract research organizations including Analytical Bio-Chemistry Laboratories, Schering-Plough Research Institute, Warner-Lambert, Pfizer, Bristol-Myers Squibb, and QPS, LLC. Currently, Dr. Ramanathan is providing leadership to the regulated bioanalytical group at Pfizer World Wide Research and Development Laboratories in Groton, CT.  He has published over 50 research papers and over 10 book chapters in pharmaceutical analysis. He is the editor of the book entitled “Mass Spectrometry in Drug Metabolism and Pharmacokinetics” (Wiley, Hoboken, NJ, 2008). In 2012 and 2013, Dr. Ramanathan co-edited peer-reviewed special Bioanalysis Journal issues focusing on “HRMS in DMPK”. Dr. Ramanathan served as the Chairperson of the North Jersey Section of ACS Mass Spectrometry Discussion Group (2005) and as the Chairperson of the ASMS Drug Metabolism and Pharmacokinetics Interest Group (2008-2010). Dr. Ramanathan was one of the inaugural organizing committee members of the APA-India Conference and contributed to APA-USA Conference by serving in the Discovery and New Technology committee over the last several years. Dr. Ramanathan’s other contributions to the scientific community include podium presentation session chairperson at EAS, ACS, ASMS, APA-India, APA-USA and CPSA-USA, short course instructor at EAS, ACS, ASMS, and APA-India, reviewer for Xenobiotica, Journal of Mass Spectrometry, Bioanalysis, Drug Metabolism and Disposition, Drug Metabolism Letters, Journal of the American Society for Mass Spectrometry, Rapid Communications in Mass Spectrometry, Journal of Pharmaceutical and Biomedical Applications, Chemical Research in Toxicology and Wiley Book Proposals.