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Professor |
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 ref09/29/2010dy 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.
Updated October 2010
“A Study of the Precision and Accuracy of Peak Quantification in Comprehensive Two-Dimensional Liquid Chromatography in Time”, J. Chromatogr. A, 2010, 1217, 4313–4327, D. F. Thekkudan, S. C. Rutan and P. W. Carr.
“Application of Snyder–Dolan classification scheme to the selection of “orthogonal” columns for fast screening of illicit drugs and impurity profiling of pharmaceuticals – I. Isocratic elution”, J. Chromatogr A, 2009, 1216, 6587–6599, W. Fan, Y. Zhang, P. W. Carr, S. C. Rutan, M. Dumarey, A. P. Schellinger, W. Pritts.
“Evaluation of the Multivariate Selectivity of Multi-way Liquid Chromatography Methods,” J. Chemom., 2007, 21, 335–345, M.T. Cantwell, S.E.G. Porter and S. C. Rutan.
“Fast Comprehensive Two-Dimensional Liquid Chromatography,” J. Chromatogr. A, 2007, 1168, 3-43, D. R. Stoll, X. Li, X. Wang, P.W. Carr, S.E.G. Porter and S. C. Rutan.
“Evaluation of the Identification Power of RPLC Analyses in the Screening for Drug Compounds”, Anal. Chem.,2010, 82, 6056–6065, M. Dumarey, Y. Vander Heyden and S. C. Rutan.
“Development of an In Vitro Incubation Procedure for Screening of CYP2D6 Intrinsic Clearance,” J. Chromatogr. B, 2007, 850, 74-82, S.E.G. Porter, R.B. Keithley and S. C. Rutan.
Books, Book Chapters
“Denoising and Signal-to-Noise Ratio Enhancement: Classical Filtering”, in Comprehensive Chemometrics, Volume 2, S. Brown, R. Tauler and R. Walczak, Eds., Elsevier: Oxford, 2009, pp. 9-24, D. F. Thekkudan and S. C. Rutan
“Two-Way Data Analysis: Multivariate Curve Resolution – Iterative Resolution Methods” in Comprehensive Chemometrics, Volume 2, S. Brown, R. Tauler and R. Walczak, Eds., Elsevier: Oxford, 2009, pp. 325-344, A. de Juan, S. C. Rutan and R. Tauler.
“Introduction to Multivariate Curve Resolution” in Comprehensive Chemometrics, Volume 2, S. Brown, R. Tauler and R. Walczak, Eds., Elsevier: Oxford, 2009, pp. 249-259, S. C. Rutan, A. de Juan and R. Tauler.
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Updated: 03/19/2012 |
