HPLC METHOD DEVELOPMENT FOR DULOXETINE HYDROCHLORIDE USING A COMBINATION OF COMPUTER-BASED SOLVENT STRENGTH OPTIMIZATION AND SOLVENT SELECTIVITY MIXTURE DESIGN

Computer simulation software for solvent strength optimization and sta tistical mixture design based on the solvent selectivity triangle were useful tools employed for the development of a reversed-phase HPLC me thod to separate duloxetine, a new anti-depressant compound, and struc turally-related impurities. Solvent strength optimization was used to show that adequate separation for all impurities could not be obtained with a single organic modifier and to aid in choosing appropriate bou ndary conditions for a mixture design study. The mixture design was us ed to obtain resolution maps for organic modifier mixtures consisting of acetonitrile, methanol, and tetrahydrofuran. Overlapping resolution maps for the peak pairs of interest revealed the solvent composition that would provide the maximum resolution. Finally, solvent strength w as optimized at the best solvent composition and information about met hod robustness obtained.