CPSA 2009

Impacting Biology through Analysis

October 26-29, 2009
Langhore, PA

Short Courses

Monday, October 26, 2009
Bucks County Sheraton Hotel
Langhorne, PA

The CPSA Short Courses focus on specialized training. These workshop-style events provide a unique opportunity to learn about current industry practices, emerging applications, and innovative analytical technologies. CPSA Short Course Instructors create a truly dynamic learning environment as key fundamentals are reviewed and first-hand experiences and practical case studies are openly discussed.

Method Development for LC/MS: Traditional Approaches and Emerging Trends

This practical course on HPLC method development for LC/MS covers the specifics of how sample preparation and HPLC methods are developed for interfacing to ESI and APCI. The course discusses the importance of HPLC when interfaced with mass spectrometry including the HPLC separation of undetected matrix components, isomers and labile metabolites. The development of HPLC methods for LC/MS for use in qualitative and quantitative analysis throughout drug discovery and drug development are presented. The most advantageous column chemistry for each LC/MS application are thoroughly discussed including, reverse phase, normal phase, ion-exchange, HILIC, monolithic and polar embedded phases. The latest technologies such as UPLC, micro-SPE and on-line SPE will also be discussed. Orthogonal approaches to extraction and chromatography to achieve optimized LC/MS methods will be presented. Step-wise method development tutorials of developing methods for specific compound classes based on the structure are included in the final summary.

Instructors:
Roger Hayes, Schering-Plough Research Institute
Shane Needham, Alturas Analytics

High Throughput Drug Discovery Support: LC/MS Strategies for Method Development, Profiling and Workflow Solutions

Integrated HPLC and MS approaches for high throughput analysis have become standard practice in a pre-clinical drug discovery setting. Successful support strategies often provide a blend of high throughput methodologies with appropriate resources (tools and personnel). This course will target the ’Äúbread and butter’Äù functions of discovery medicinal chemistry support. Real-world experiences with method development and analytical support will be discussed. Examples that feature ultra high throughput (library-based formats and individual sample processing), fast LC (theory & practice), generic gradient RP method strategies , scaling for HT purification, building in robustness into LC/MS set ups, details and perspectives on open-access success, fast physico-chemical profiling of compounds, and IT based workflow solutions.

Instructors:
Mark Hayward, Lundbeck Research USA
Ken Lewis, OpAns

Is Poor Bioavailability in Early drug Discovery a Problem and If So, How Can We Solve It?

Poor oral bioavailability is one of the leading causes of compound failure in preclinical and clinical development. Compounds with poor oral bioavailability have low plasma exposure and tend to demonstrate high inter-individual variability, which can limit their therapeutic application. Poor oral bioavailability in preclinical species does not necessarily translate into poor human oral bioavailability. This practical/hands-on course is designed to increase participants knowledge of:

The parameters that determine drug oral bioavailability
The factors that lead to species differences in oral bioavailability and how to deal with them
Approaches for optimizing the physicochemical parameters that influence drug solubility/permeability and metabolism
The workshop will also include a hands-on session that aims at improving your ability to apply these strategies to medicinal chemistry for hit selection, lead optimization and development candidate selection

Targeted Audience: Medicinal Chemists, Discovery Biologists, ADME Scientists

Instructor:
Ayman El-Kattan, Pfizer

Analysis of Peptides and Proteins: Sample Preparation to Identification to Quantitation

Within the last decade, nanoscale liquid chromatography-tandem mass spectrometry (nLC-MS/MS) has revolutionized the identification of proteins and peptides in biological matricies. The technology has developed from being a purely qualitative tool for (global) proteomics to a quantitative method suitable for peptide/protein biomarker validation. Key to success has been the combination of highly specific sample preparation methods, high sensitivity nanospray ionization, and high performance mass spectrometry. In this short course, critical parameters involved in robust sample preparation, nanobore LC and nanospray along with their analytical benefits will be emphasized. The transition of the traditionally qualitative nLC-MS/MS technology to those suitable for absolute quantification will be discussed. Real world examples from the literature will be presented. The target audience includes both analysts that have been engaged in qualitative proteomics wishing to transition to quantitative analysis and small molecule quantitative analysts wishing to learn more about the challenges specific to peptide/protein quantification.

Instructors:
Nalini Sadagopan, Agilent Technologies
Gary A. Valaskovic, New Objective
Chuck Witkowski, Protein Discovery

Fundamentals of Structural Characterization by NMR

The "Fundamentals of Structural Characterization by NMR" short-course will cover the essentials of both 1H and heteronuclear NMR as applicable to structural problems in the organic chemistry environment. This will be a hands-on, focused discussion. We will begin with a quick discussion of the fundamental aspects of the NMR experiment that have a direct impact on the final spectra and proceed through the basics of 1D NMR interpretation. Subsequent sections will focus on a particular type of experiment (e.g., Nuclear Overhauser Experiments, proton-proton coupling experiments, proton-carbon coupling experiments, etc.). The information available from each type of experiment will be discussed using examples and case studies. Each segment will build on the previous material and grow into a complete discussion of comprehensive assignment strategies for small molecule NMR problems.

Instructor:
David J. Russell, Varian