title: Prediction and mechanism elucidation of analyte retention on phospholipid stationary phases (IAM-HPLC) by in silico calculated physico-chemical descriptors.
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 kWIAMvalues. 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 kWIAM. 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 kWIAMvalues of any molecule included in the PubChem database, which is freely available at http://nova.disfarm.unimi.it/logkwiam.htm.
authors.affiliation: Department of Pharmacy, Università degli Studi di Napoli Federico II, via D. Montesano 49, I-80131 Naples, Italy. Electronic address: giacomo.russo@unina.it.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Russo
authors.affiliation: Department of Pharmacy, Università degli Studi di Napoli Federico II, via D. Montesano 49, I-80131 Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Grumetto
authors.affiliation: Department of Pharmacy, Università degli Studi di Napoli Federico II, via D. Montesano 49, I-80131 Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Barbato
authors.affiliation: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via L. Mangiagalli 25, I-20133 Milan, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Vistoli
authors.affiliation: Department of Pharmaceutical Sciences, Università degli Studi di Milano, via L. Mangiagalli 25, I-20133 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pedretti
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008567:Membranes, Artificial; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D055672:Static Electricity; D014867:Water / Q000737:chemistry
chemical_list: D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010743:Phospholipids; D014867:Water; D020003:1-Octanol
keywords: Biochromatography; IAM-HPLC; Immobilized artificial membrane; Prediction of phospholipid affinity; Quantitative structure-property relationship models