Novel computational approaches to retention modeling in dual hydrophilic interactions/reversed phase chromatography

Abstract

The mixed-mode chromatographic behavior was estimated for imidazoline and serotonin receptor ligands, and their related compounds on dual hydrophilic/reversed phase stationary phase. The Box-Cox transfor- mation was used to obtain the most suitable mathematical equations which describe the mixed-mode retention. Optimal equations were found for the optimization parameter ( λ): λ= -1, λ= -0.5, λ= 0, λ= 0.5, and λ= 1. The proposed equations show satisfactory characteristics compared to standard mul- timodal and quadratic approaches. For a wide range of volume fractions of the mobile phase modifier, crossing between hydrophilic and reversed phase interactions (the turning point) was defined in terms of the minimal retention and the minimum value of the volume fraction of the aqueous eluent in the mobile phase. The cubic spline inter- polation was used as a reference method for estimation of the turning point. It was found out that the newly proposed equations can be used as alternative mathematical forms for the description of the dual retention mechanism and for the evaluation of the turning point. Three new experimental descriptors of the mixed-mode retention were proposed. Two descriptors quan- titatively characterize hydrophilic (log k H ) and reversed phase (log k R ) interactions, while the third one (log k A ) refers to the average retention for the whole HILIC/RP range. It was established that the main fac- tors which control dual nature of the mixed-mode retention are lipophilicity, dipol-dipol, van der Waals and hydrogen bonding interactions. It was concluded that the newly proposed estimations of the retention data reliably characterize the mixed-mode chromatographic behavior.