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

Russo, Giacomo; Grumetto, Lucia; Barbato, Francesco; Vistoli, Giulio; Pedretti, Alessandro


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


Russo, G., Grumetto, L., Barbato, F., Vistoli, G., & Pedretti, A. (2017). Prediction and mechanism elucidation of analyte retention on phospholipid stationary phases (IAM-HPLC) by in silico calculated physico-chemical descriptors. European Journal of Pharmaceutical Sciences, 99, 173-184.

Journal Article Type Article
Acceptance Date Nov 28, 2016
Online Publication Date Dec 3, 2016
Publication Date Mar 1, 2017
Deposit Date Mar 31, 2020
Journal European Journal of Pharmaceutical Sciences
Print ISSN 0928-0987
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 99
Pages 173-184
Keywords Immobilized artificial membrane; Prediction of phospholipid affinity; IAM-HPLC; Quantitative structure-property relationship models; Biochromatography
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