Prediction and mechanism elucidation of analyte retention on phospholipid stationary phases (IAM-HPLC) by in silico calculated physico-chemical descriptors

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Giacomo Russo, Lucia Grumetto, Francesco Barbato, Giulio Vistoli, Alessandro Pedretti
The present study proposes a method for an in silico calculation of phospholipophilicity. Phospholipophilicity is intended as the measure of analyte affinity for phospholipids; it is currently assessed by HPLC measures of analyte retention on phosphatidylcholine-like stationary phases (IAM – Immobilized Artificial Membrane) resulting in log kW^IAM values. Due to the amphipathic and electrically charged nature of phospholipids, retention on these stationary phases results from complex mechanisms, being affected not only by lipophilicity (as measured by n-octanol/aqueous phase partition coefficients, log P) but also by the occurrence of polar and/or electrostatic intermolecular interaction forces. Differently from log P, to date no method has been proposed for in silico calculation of log kW^IAM.The study is aimed both at shedding new light into the retention mechanism on IAM stationary phases and at offering a high-throughput method to achieve such values. A wide set of physico-chemical and topological properties were taken into account, yielding a robust final model including four in silico calculated parameters (lipophilicity, hydrophilic/lipophilic balance, molecular size, and molecule flexibility). The here presented model was based on the analysis of 205 experimentally determined values, taken from the literature and measured by a single research group to minimize the interlaboratory variability; such model is able to predict phospholipophilicity values on both the two IAM stationary phases to date marketed, i.e. IAM.PC.MG and IAM.PC.DD2, with a fairly good degree (r²=0.85) of accuracy.The present work allowed the development of a free on-line service aimed at calculating log kW^IAM values of any molecule included in the PubChem database, which is freely available at http://ift.tt/2hu7KXF.

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