CPSA Digest 2001

Proceedings -Tuesday, October 9, 2001

TuOB1

Structure Profiling:
Chemical Structure Based Software Tools for Metabolite Identification

Background:
Scientists at Eastman Kodak previously reported the development of a component detection algorithm, CODA, for noise and background reduction in LC/MS chromatograms (1). This was achieved using a variable selection procedure that selects mass chromatograms with low noise and low background contribution, then recombines the mass chromatograms to provide a reduced total ion chromatogram or optionally, overlay plots. Recently a second algorithm, CompareLCMS, was developed to distinguish dissimilarities in CODA reduced chromatograms permitting the extraction of component differences in similar LC/MS data sets (2). These targeted applications require program distribution to site wide desktops, a user-friendly interface, and file format support for a variety of MS vendors. These needs were achieved through collaboration with Advanced Chemistry Development, ACD.

ACD (Advanced Chemistry Development) is a leading developer of chemical property prediction and spectral prediction and database management software. The overall strategies for ACD software are:

1. To go from spectrum to structure as fast as possible, utilizing database searching and structure verification
2. To extract the highest quality spectrum
3. Reporting
4. To make use of additional information with integration to other technologies (e.g., NMR, UV/Vis, Chromatography).

Premise:
Multiple software offerings work together to address the following areas: Sum CODA (Component Detection Algorithm) software version 5.0 combines knowledge of chromatography and mass spectral data to reduce noise Sum CompareLCMS software version 5.0 detects changes between samples, e.g., different matrices and different time frames. Sum Fragment-based prediction software verifies metabolite chemical structures Sum Structure-based spectroscopic databases build a knowledge base Sum Spectroscopy software elucidates the chemical structures of metabolites.

Value of the Technology
CODA provides automated data reduction for the R&D synthetic chemist using walk-up LC/MS for routine peak purity and molecular weight information needs. CODA provides significant time savings by permitting complete visualization, (mass, intensity, and time) of the 3-D LC/MS data sets versus the traditional 2-D total ion chromatograms. CompareLCMS is robust in comparative LC/MS studies including formulation stability, synthetic discovery and optimization, reverse engineering, metabolite identification, and fundamental studies involving chemical interactions.

The tools and processes described in this presentation address the data-handling bottleneck in many LC/MS operations. Based on demonstrated efficiency gains, full implementation of this strategy can permit continued growth in certain LC/MS applications using existing resources.

Links
Advanced Chemistry Development

Press Releases: www.acdlabs.co.uk/publish/press_release.html

1. W. Windig, J.M. Phalp, A.W. Payne, "A Noise and Background Reduction
Method for Component Detection in Liquid Chromatography/Mass Spectrometry," Anal. Chem., 68, 1996, 3602-3606.

2. W. Windig, W.F. Smith, W.F. Nichols, "Fast Interpretation of Complex LC/MS Data Using Chemometrics", Anal. Chim. Act., in press

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