Dr Giacomo Russo G.Russo@napier.ac.uk
Lecturer
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
Authors
Lucia Grumetto
Francesco Barbato
Giulio Vistoli
Alessandro Pedretti
Abstract
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://nova.disfarm.unimi.it/logkwiam.htm.
Citation
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. https://doi.org/10.1016/j.ejps.2016.11.026
| 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 |
| DOI | https://doi.org/10.1016/j.ejps.2016.11.026 |
| Keywords | Immobilized artificial membrane; Prediction of phospholipid affinity; IAM-HPLC; Quantitative structure-property relationship models; Biochromatography |
| Public URL | http://researchrepository.napier.ac.uk/Output/2649506 |