CPSA USA 2014

Short Course 1 - Princeton 1 Ballroom
Protein ID and Biomarker Analysis by Mass Spectrometry: Challenges and Solutions for Quantification and Differential Analysis

Mass spectrometry, as enabled by modern ionization methods such as MALDI and ESI, has dramatically transformed the science of protein identification and quantification. There is a rapidly growing demand for the quantitative analysis of proteins and peptides by LC-MS/MS in the bio-analytical and clinical laboratories. This short course will help attendees deeply appreciate specific challenges associated with successful outcomes in LC-MS based protein analysis. An in-depth view of the practical aspects involved in protein/peptide analysis by LC-MS/MS will be covered and will include case studies from the literature and from the instructor's personal experiences.

The use of nanospray enabled LC-MS has developed from a qualitative tool for (global) proteomics to a quantitative method suitable for activities such as peptide/protein biomarker validation. Key to success has been the combination of highly specific sample preparation methods, high sensitivity nanospray ionization, and high performance tandem mass spectrometry. Critical parameters involved in robust sample preparation, nanobore LC and nanospray, sensitive & selective MS detection along and their analytical benefits will be emphasized. The transition of the qualitative nLC-MS/MS technology to methods suitable for absolute quantification will be discussed. New tools for cloud based data sharing and the underlying principles for biomarker identification and validation by differential mass spectrometry will be presented. Real world examples will be presented. The course will also feature an additional hands-on "connections workshop" to hone your expertise is making high quality LC-MS fluid connections.

The target audience includes analysts that have been engaged in qualitative proteomics wishing to transition to quantitative methods, analysts that have specialized in small molecule quantification, and those involved in the development of methods for clinical outcomes.

Instructors:
Nalini Sadagopan, Agilent Technologies
Gary Valaskovic, New Objective
Nathan Yates, University of Pittsburgh

Short Course 2 - Princeton II Ballroom
New! LC-MS Regulated Bioanalysis for Large and Small Molecules: Methods, Practices, Technologies and Instrumentation

This course gives an overview of the methods, practices, technologies and instrumentation used to perform LC-MS in the regulated bioanalytical laboratory. Along with an introduction of LC-MS fundamentals, the course will give step-wise method development and validation schemes for small and large molecule LC-MS method development. Current validation and development expectations from the latest white papers will be presented for discussion. Sample preparation techniques such precipitation, SPE, SLE and LLE will be discussed. For large molecule LC-MS/MS bioanalysis, a "bottom-up" digestion approach will be presented. Specific examples on how to avoid the pitfalls of ion-suppression will be presented. This course will feature a dynamic format where the latest technology in MFLC, UPLC and the advantages of the latest LC-MS instruments will be highlighted. A portion of the course will be devoted to, "validating LC-MS instruments for "21 CFR Part 11" compliance. At the end of the course, a method development tutorial for particular molecules will be presented to the participants.

Instructors:
Shane Needham, Alturas Analytics
Jim Shen, Bristol-Myers Squibb
Dave Abramowitz, AB SCIEX

Short Course 3 - Lehigh
Human Pharmacokinetic Prediction and Approaches to Identify Rate Determining Step of New Chemical Entities: Industrial Perspective

Poor oral bioavailability is one of the leading causes of compound failure in preclinical and clinical development. Compounds with poor oral bioavailability and short half life tend to have large dose and higher inter and intra-individual variability, which would limit their therapeutic usefulness and increase the cost of their developments. Poor oral bioavailability in preclinical species does not necessarily translate into poor human oral bioavailability and vice versa. This practical/hands on course is specifically designed for personnel in the pharmaceutical and biotechnology industries and contract research organizations (CROs), who need to understand:

• General principles of pharmacokinetics
• The parameters that determine oral bioavailability in human
• Approaches to optimize physicochemical and biopharmaceutical parameters that
• influence drug solubility, permeability, and metabolism, where applicable
• Anatomical and physiological factors that lead to species differences in oral
• bioavailability
• The state-of-the-art in vitro and in vivo ADME assays, and how pharmacokinetics, and drug metabolism and transporter research studies are conducted to select the candidates to advance in preclinical and clinical development
• The utility of validated physiologically based pharmacokinetics (PBPK) modeling during discovery and development of drug candidates
• The use of Biopharmaceutics Drug Disposition Classification System (BDDCS) in predicting drug disposition, drug-drug interaction, and impact of food on the pharmacokinetic profile of new chemical entities (NCEs)
• 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

Instructor:
Ayman El-Kattan, Pfizer

Short Course 4
New! Building a Better Clinical Mass Spectrometry Lab

Instructors:
Timothy Garrett, University of Florida
Mark Hayward, Active Ingredient Technologies
Kenneth Lewis, Opans

Opening Remarks
Timothy Garrett, University of Florida

MS to Screen Multiple Metabolites – How You Design and Validate for Population Screening in the Hands of Non-Clinical Chemists and Non-Mass Spectrometrists
Donald Chace, Pediatrix Analytical

Case Studies in Start Ups and Scale Ups of LC/MS Drug Testing Labs: Challenges and Solutions in Achieving Sufficient Capability and Effective Workflows
Mark Hayward, Active Ingredient Technologies

Some Thoughts on Biomarker Translation
Randall Nelson, Arizona State University

Break

Enabling Sensitivity and Ease-of-Use Through Nanospray Integration
Gary Valaskovic, New Objective

Challenges of Quantitative Dried Blood Spot Analysis from the Clinic
Kenneth Lewis, OpAns

Strategies for Developing and Implementing Initial LC-MS-Based Biomarker Assays in Drug Discovery
Timothy Olah, Bristol-Myers Squibb