The control of genotoxic impurities (GTIs) is a crucial activity that is performed for any new chemical entity intended for clinical use. A key element of this is the quality risk assessment. This article seeks to examine the primary components of such a strategy, focusing specifically on the effective use of in silico assessment tools to augment this process, in particular the calculation of theoretical purge factors based on the physicochemical properties of a specific GTI and its interrelationship to the process.
Supercritical fluid chromatography was utilized in combination with the Abraham model of linear solvation energy relationship to characterize 11 different HPLC stationary phases. System constants were determined at one supercritical fluid chromatography condition for each stationary phase. The results indicate that several types of silica columns, including type B silica, type C silica, and fused core silica, are very similar in their retention behavior. Several aromatic stationary phases were characterized and it was found that, in contrast to the other phases studied, all of the aromatic stationary phases had positive contributions from the dispersion/cavity (v) term of the linear solvation energy relationship. Several aliphatic phases were characterized and there were several linear solvation energy relationship constants that differentiated the phases from each other, mainly the polar terms (dipolarity and hydrogen bonding). One stationary phase, a fused core pentafluorophenyl (PFP) phase, had very poor regression quality. The column volume of this phase was lower than the others in the study, which may have had some impact on the results of the regression.
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