Proceedings

Day 2 - Wednesday, September 27, 2000

WOA
Drug Discovery in the Post-Genome Era (Proteomics/Genomics)

The completion of the Human genome sequence has created a wealth of information and its utility to understand disease processes is causing a paradigm shift in early phase drug discovery research. Biological mass spectrometry is making major contributions to the burgeoning fields of Genomics and Proteomics, enabling the exploitation of the genome and the proteome, thereby enhancing the understanding of disease processes and the development of novel therapies. The session focused on, i) genotyping by mass spectrometry and it's use in drug discovery and development process, ii) linking transcriptional profiling to the proteome to identify cancer screening markers and iii) tools and techniques available to perform high-throughput proteomics and their utility in early-phase drug discovery.

High Throughput Genotyping by Mass Spectrometry

Diagnostic Discovery of Ovarian Cancer Screening Markers: Linking the Proteome to the Transcriptome

High Throughput Protein Identification by Mass Spectrometry

Roundtable Discussion 5

WOB
Predictive Models for Lead Optimization and Selection

The increased number of pharmacologically active compounds identified in the drug discovery process has placed great demands on rapid screening and selection of compounds with favorable human pharmacokinetic and safety protocols. Early determinations of pharmaceutical properties can serve as predictors of a compoundís likely development success. Access to this valuable information can help to identify candidates with inadequate properties as well as to provide insights to guide synthetic optimization. Ultimately, discovery to market attrition may be minimized by selecting those compounds with a higher likelihood of development success. This session discussed the application of predictive profiling throughout the drug discovery-development continuum as well as implementation of such an approach within drug discovery.

Detection of Oligonucleotide Ligand Complexes by ESI-MS (DOLCE-MS) as a Component of High Throughput Screening

In Vitro Profiling for ADME Characteristics in Support of Drug Discovery

Evolving LC/MS Predictive Profiling Protocols to Speed Pharmaceutical Development

Implementation of Pharmaceutical Profiling in Drug Discovery

Roundtable Discussion 6

WOC
Vendor/Exhibitor Session:
Mass Spectrometry and Data Management

Although 96 well plates are the first line of approach for increasing throughput, leachates from the plates may interfere with sample analysis. The first part of this session investigated methods for reducing leachates. A second challenge, and one that is certainly not limited to LC/MS/MS, is that of electronic signatures. The second part of this session dealt with compliance with 21CFR Part 11, and included discussions on how paperless a lab can or should be.

Reduction of Leachates From 96 Well Plates

21CFR Part 11: How Paperless Can/Should We Be?

Roundtable Discussion 7

WOD
Mass Spectrometry in the QC Laboratory: Are We Ready?

The complementary mass spectrometric techniques of MALDI-TOF and API-ESI emerged as the pre-eminent methods for the unambiguous characterization of small molecular and biomolecular pharmaceuticals in the 1990s. API-ESI-MS, either as a stand-alone method or in combination with high performance liquid chromatography, is poised to enter the QC lab as we begin the new millennium. The challenges presented in developing, validating, transferring and implementing mass spectrometry in the QC environment as well as using this technology as a QC release test was the focus of " MS in the QC Lab: Are We Ready?".

Analysis of Proteins by ESI-MS in a QC Environment

Patterns in QC - (II) Matching Mass Spec Peptide Maps for Identity Testing

Roundtable Discussion 8

WOE
Purification Systems for Combinatorial Chemistry

This session explored the current status and possible future direction of mass spectrometry (MS) directed compound purification systems. The session started with an overview of what is perhaps the current state of the art approach in commercially available systems, FractionLynx from Waters/Micromass. A potentially significant enhancement to the separation part of this approach was the use of prep scale supercritical fluid chromatography (SFC) instead of the commonly used reverse phase prep-LC. Finally, a prep-LC/UV approach was described that collected only a single fraction per sample by using automated fast analytical scale LC/DAD/MS data to set the LC/UV collection parameters.

FractionLynx for CombiChem Purification

SFC/MS for CombiChem Purification

Using Analytical LC/MS to Automatically Feed Parameters into Prep LC/UV for Production CombiChem Purification

Roundtable Discussion 9

Poster Session

A Molecular Structure Based System for LC Simulation
Michael McBrien, Antony Williams, Eduard Kolovanov
Advanced Chemistry Development Inc., Toronto, Ontario, Canada

Applications of Physical Property Prediction Software to the Screening of Combinatorial Libraries (LogP, pKa, LogD and associated properties)
Antony Williams, Eduard Kolovanov, Maria Foster
Advanced Chemistry Development Inc., Toronto, Ontario, Canada

An Integrated Software System for Spectral Management for NMR, MS, IR and UV-VIS and Chemical Structures
Antony Williams, Andrey Bogomolov, Alexey Pastutsan, Vitaly Lashin
Advanced Chemistry Development Inc., Toronto, Ontario, Canada

High Throughput Analysis for Synthetic Compounds using Automated MS- and UV-Trigged High Throughput Purification System
L. Zang, R. Chen, K. Deguchi
Hitachi Instruments, Inc., San Jose, CA

Ballistic Gradient HPLC Coupled with ESI-TOF/MS for High Throughput, High Resolution Analysis of Combinatorial Chemistry Libraries
Shawn Duffy¹, Kerry Nugent¹, Wayne Scott¹, David Hawke², and Kerry Spear³
1 Michrom BioResources, Auburn CA
2 Applied Biosystems, Foster City CA
3 ICAGEN, Research Triangle Park, NC

2D HPLC as an Alternative to 2D PAGE for Protein Isolation Prior to Digestion and Proteomic Characterization by NanoLC/MS/MS
Wayne Scott¹, Shawn Duffy¹, Kerry Nugent¹, Tanuja Chaudhary², Iain Mylchreest², David Kage², Jenny Kung³, Anthony Martinez³, and Suzanne Miyamoto³
1 Michrom BioResources, Auburn CA
2 Thermoquest, San Jose CA
3 UCDCC, Sacramento, CA

Powercurve: A New Calibration Curve Fitting Procedure
Ebi Kimanani, Jean Lavigne, Lorella Di Donato, and Robert Masse
MDS Pharma Services, Quebec, Canada