USE OF COMPUTER-SIMULATIONS IN THE DEVELOPMENT OF GRADIENT AND ISOCRATIC HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY METHODS FOR ANALYSIS OF DRUG COMPOUNDS AND SYNTHETIC INTERMEDIATES

DryLab G/plus and DryLab I/plus (LC Resources) are shown to be effective aids in the development and optimization of gradient and isocratic HPLC conditions for the assay of drug substances and related compounds. Data obtained after two experimental runs in the laboratory are entered into the appropriate program where HPLC conditions can be altered (e.g. flow-rate, column dimensions, mobile phase composition, gradient steepness and shape, etc.) to arrive at optimum separation conditions with less analyst time required. The computer simulations from DryLab G/plus are shown to be suitably accurate under ''real life'' conditions in the development of gradient purity methods for two drug substances (Zalospirone and WY-47 384) and two synthetic intermediates (cyclooctatetraene and 2-methylcarboxybenzaldehyde). Moreover, DryLab I/plus was shown to be accurate in predicting isocratic retention for the separation of impurities in cyclooctatetraene, both in scaling down to small columns for speed and scaling up to a semi-preparative separation for isolation of impurities.