Computer-assisted method development and optimization in high-performance liquid chromatography.
This paper reports the use of DryLab, a computer simulation software package, to assist in the development and optimization of a reversed-phase high-performance liquid chromatographic (HPLC) method for the separation of a model drug candidate and its degradation products. Prior to the optimization process, columns with various bonded phases are evaluated for their chromatographic performance using the sample of interest. Simultaneous optimization of two separation variables and the use of resolution maps to predict the optimal conditions are illustrated. Options to optimize column conditions (column length and flow-rate) to further reduce run time are briefly discussed. The accuracy of DryLab-predicted retention times and resolution is compared with experimental values. The DryLab software used in this study provided satisfactory predictions for the selected model, with average errors of less than 3.5 and 11.8% for retention time and resolution, respectively.
Department of Pharmaceutical Research and Development, Merck Frosst Canada & Co., P.O. Box 1005, Pointe Claire-Dorval, Quebec, Canada H9R 4P8. thanh_hoang@merck.com
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TH
Hoang
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Cuerrier
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McClintock
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Di Maso
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003198:Computer Simulation