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Sarah C. Rutan

Professor Analytical chemistry (804) 828-7517 srutan@vcu.edu

http://www.people.vcu.edu/~srutan/

Education

B.S., Bates College
M.S., Washington State University
Ph.D., Washington State University

Research interests

Characterization of drug metabolism using chemometrics

Traditionally, metabolic studies have been limited to the characterization of single pathways, and the complex relationships between overlapping and competing metabolic reactions are not considered. This project is focused on the development of approaches for identifying metabolic pathways, following metabolite dynamics, and quantifying rate constants in complex reaction systems. Due to their central roles in the metabolism of many endogenous and exogenous compounds, the enzymes cytochrome P450 and uridinediphosphoglucuronosyl-transferase are of primary interest. Drugs such as dextromethorophan and illicit amphetamines are currently under investigation. Liquid chromatography coupled with UV-visible and mass spectrometric detection are used to analyze the small molecule substrates, and the corresponding intermediates and products. The kinetics for all reaction pathways are quantified using an alternating least squares algorithm. Future studies will include single enzymes, and enzyme and substrate mixtures of increasing complexity. These studies are leading to new mechanistic insights regarding the interactions among simultaneous enzymatic pathways, as well as providing a fundamental understanding of the methodologies required for the analysis of a broad range of complex metabolic pathways.

Investigations of solvation using property modulation

Acetonitrile/water and methanol/water mixtures are far and away the most commonly used solvent systems in reversed phase liquid chromatography. The goal of this project is to achieve an improved understanding of these liquids and their solvation interactions with compounds that need to be separated, leading to quantitative prediction of the separation characteristics of a liquid chromatography method. Although these solvent mixtures have been studied extensively in the past, a detailed understanding of the interactions in these liquids is still lacking. In this work, a suite of complementary methodologies are used to characterize these mixtures by modulation of a number of the experimental conditions, including mole fraction composition of the mixtures, temperature, and solute identity and concentration. Infrared spectroscopy, with both transmission and attenuated total ref09/28/2006dy these mixtures. The resulting spectra are analyzed using several techniques, including two-dimensional correlation analysis and alternating least squares analysis, to elucidate structural information about the components in the mixtures. These results are analyzed in the context of several theoretical and simulation techniques, including ab initio structure calculations, and Monte Carlo and cellular automata simulations.

Selected recent publications

1. “Multivariate Curve Resolution with Non-linear Fitting of Kinetic Profiles,” Chemom. Intell. Lab. Sys., 2001, 59, 19-31, E. Bezemer and S.C. Rutan.
2. “Principles and Applications of Solvatochromism,” Appl. Spectrosc., 2001, 55, 362A-372A, S. Nigam and S.C. Rutan
3. “Study of Complexation in Methanol/Water Mixtures by Infrared and Raman Spectroscopy and Multivariate Curve Resolution-Alternating Least Squares Analysis,” Appl. Spectrosc., 2003, 57, 483-490, C.A. Holden, S.S. Hunnicutt, R. Sánchez-Ponce, J.M. Craig and S.C. Rutan.
4. “Evaluation of Synthetic Liquid Chromatography-Diode Array Detection-Mass Spectrometry Data for the Determination of Enzyme Kinetics,” Anal. Chim. Acta, 2003, 2003, 490, 17-29, E. Bezemer and S.C. Rutan.
5. “Studies of Liquid Phase Complexes in Acetonitrile/Water Solutions by ATR-IR Spectroscopy with Acetaldehyde as a Model Solute,” Appl. Spectrosc., 2004, 58,1187-1194, N. Fillipan, E. Bezemer, J. Burke and S.C. Rutan.
6. “Steady State Kinetic Model Constraint for Multivariate Curve Resolution – Alternating Least Squares Analysis,” Chemom. Intell. Lab. Sys., 2005, 77, 50-58, R. Sánchez-Ponce and S.C. Rutan.
7. “Analysis of Three- and Four-way Data Using Multivariate Curve Resolution-Alternating Least Squares with Global Multi-way Kinetic Fitting,” Chemom. Intell. Lab. Sys., 81 (2006) 82-93, E. Bezemer and S.C. Rutan.
8. “Analysis of Four-Way Two-Dimensional Liquid Chromatography-Diode Array Data: Application to Metabolomics,” Anal. Chem., 78 (2006) 5559-5569, S.E.G. Porter, D.R. Stoll, S.C. Rutan, P.W. Carr and J.D. Cohen.

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