Proceedings

Day 1 - Tuesday, September 26, 2000

TuOA
Plenary

Proteomics Using Multidimensional Chromatography and Tandem Mass Spectrometry

TuOB
New Technologies and Approaches for Drug Metabolism

Mass spectrometry has long been recognized for its contribution to metabolite profiling and structural identification. The advent of high duty cycle mass analyzers, such as ion traps and Q-TOF instruments, has led to new applications and strategies for in vitro and in vivo assessment of drug biotransformation. Concurrent with these advances has been a pervasive trend towards expanded metabolite profiling earlier along the drug discovery/development timeline. This in turn has led to new bottlenecks imposed by data mining, interpretation and reporting. Initial work by practitioners combined with the collaborative support of vendors has led to a number of innovative solutions to these problems. In this session, we gain the perspective of both parties on issues relating to both MS hardware and software.

Metabolite Profiling/ID: In Vitro and In Vivo Metabolism

Software/Hardware for Metabolite Profiling/ID

Roundtable Discussion 1

TuOC
Vendor/Exhibitor Session:
Sample Preparation & Chromatography

Pharmaceutical LC-MS laboratories continually search for new sample preparation and chromatographic techniques to increase sample throughput and reduce the time required to get a drug to market. This session presents a critical overview of state-of-the-art sample preparation techniques, including off-line automated 96-well plates and online techniques such as the Prospekt system and turbulent flow chromatography. Future directions, including fast chromatography, "grand trays", and microchip separations were also described.

Automated Sample Preparation in High Throughput LC-MS/MS Analysis

Sample Preparation for LC-MS/MS Analysis - On-line versus Off-line

High-Throughput SRM LC/MS Analyses:
From 384 Multi-Well Plates to Chips

Roundtable Discussion 2

TuOD
Structure and Purity Determination: How Much and When?

The increased pressure to keep pace with high throughput sample generating technologies such as automated parallel synthesis has created unique challenges for structure and purity determination. Selection of instrumentation and development of the analytical method is dependent on the "how much and when?" requirements of the specific drug development stage. This session explored the issues, needs, and preliminary benchmarks with regard to lead identification, lead confirmation, and purification.

Using Fluorometric Microvolume Assay Technology (FMAT) for Lead Identification and Characterization in High Throughput Drug Screening

High Resolution FTMS for High Throughput Structural Characterization

High Throughput Purification

Roundtable Discussion 3

Poster Session

A Comparative Study of Parallel Artificial Membrane Permeability Assay for Passive Absorption Screening
Chengyue Zhu, Teng-man Chen, Kinkai Hwang
Aventis Pharmaceuticals, Bridgewater, New Jersey

Determination of Drug Permeability by Filter-Immobilized Artificial Membranes and Detection by LC/MS
E. H. Block¹, A. Avdeef², M. Strafford², B. Kenney¹, M. Balogh¹, K. Yu¹
1 Waters Corporation, Milford, MA 01757
2 pION, Inc. Woburn, MA 01801

Speeding Metabolic Stability Assays Using Automated, High Throughput LC/MS Techniques
K. Johnson¹, J. Erve², A. Dandeneau², M. Swartz¹, B. Kenney¹
1 Waters Corporation, Milford, MA 01757
2 GENTEST Corporation, Woburn, MA 01801

Pharmacokinetic (PK) screening using high throughput sample preparation with a TECAN robotic sample processor (Genesis 150) followed by On-line Extraction- HPLC/MS/MS
Hideji Fujiwara, J. Randy McKee, Kevin L. Duffin
Pharmacia Co, St. Louis, MO

Applications of High-Throughput Pharmaceutical Analysis using A Parallel Turbulent flow chromatography / Tandem mass spectrometry (TFC-MS/MS) System
Daniel J. Magiera, Joe Takarewski, John Brann, Hubert M. Quinn
Cohesive Technologies Inc., Franklin, MA

Strategies for High-Throughput: Multi-Stream Serial LC/MS
Byron Kieser, Yves Leblanc, Tanya Gamble
Applied Biosystems MDS SCIEX, Concord, Ontario, Canada

Accelerated Selection of Lead Candidates Using Isolated Blood Perfused Organs with LC/MS/MS Analysis
C. Gerald Curtis¹, M. Helen Hughes¹, Kumar Ramu², Ben Chien²
1 Bowman Research (UK), Newport, Gwent, UK
3 Quest Pharmaceutical Services, Newark, DE

Automated High Throughput Open Access LC/MS Reaction Monitoring in a Discovery Pharmaceutical Environment
Larry M. Mallis¹, Ani Sarkahian¹, William L. Watts, Jr.¹, Kate Bathurst², George P. Hammond VI², John Van Antwerp³, Ed Aig³, Ronan Cleary⁴
1 Discovery Analytical Chemistry, Chemical Sciences, Wyeth-Ayerst Research, Radnor, PA
2 Computer Support, Radnor, PA
3 Waters Corporation, Morristown, NJ 07960
4 Waters Corporation, Milford, MA 01757

TuOE
Evening Session

How to Demo/Purchase an LC/MS Instrument: Experiences and Perspectives

LCMS instrumentation has become ubiquitous in pharmaceutical laboratories. The proper choice of the most suitable LCMS is important whether the instrument is the first purchase or an addition to an existing facility. In this session, a diverse group of LCMS users and manufacturer representatives answered the following questions based on their personal experiences:

1. What are the most important criteria to use when making an LCMS purchase?
2. How do you structure a demo to obtain the most important information required for making a decision on an LCMS purchase?
3. What pitfalls should be avoided?

Tony Brand, Agilent Technologies
Ashok R. Dongre, Bristol-Myers Squibb
Tom Driscoll, Micromass
Mark J. Hayward, Novartis
Patrick J. Rudewicz, Schering-Plough Research Institute