IAM retention and blood brain barrier penetration

Relationships between human intestinal absorption and polar interactions drug/phospholipids estimated by IAM–HPLC.

“…This occurs because, differently from the interaction forces in noctanol/water partition systems, the recognition forces involved in the interactions with phospholipids include ionic bonds (Taillardat-Bertschinger et al, 2003;Vrakas et al, 2008). The latter can be estimated by interpolating lipophilicity values in n-octanol and phospholipid interaction data, according to a simple procedure we proposed in our recent works (Grumetto et al, 2012(Grumetto et al, , 2013(Grumetto et al, , 2014 (Grumetto et al, 2012(Grumetto et al, , 2013(Grumetto et al, , 2014, but did not with either log D or logk IAM W values, in contrast with other authors (Ducarme et al, 1998;Kepczy nska et al, 2000;Péhourcq et al, 2004;Reichel and Begley, 1998;Salminen et al, 1997). This suggests that, despite ionic bonds enhance partition in phospholipids, they act as "trapping" forces at the membrane level, hindering its permeation.…”

Brainpeps: the blood–brain barrier peptide database

“…Following this, the solution is centrifuged and the content in the aqueous phase is determined using high-performance liquid chromatography (HPLC). The content in the organic phase is also determined with HPLC after lyophilizing and reconstitution in methanol (Ducarme et al 1998). The octanol/buffer coefficient is finally calculated as the ratio of the concentration in the octanol layer to that in the buffer layer.…”

“…IAM columns contain a monolayer of phosphatidylcholine covalently immobilized on a silica support, which mimics very closely the lipid membrane bilayer (Ducarme et al 1998;Ecker and Noe 2004;Reichel and Begley 1998). Given the chemical and physical similarity between these IAM columns and the biological cell membranes, these chromatographic columns are mainly used for predicting biomembrane transport properties (Cucullot et al 2006;Lazaro et al 2005).…”

Determination of lipophilic descriptors of antihelmintic 6,7‐diaryl‐pteridine derivatives useful for bioactivity predictions

“…The immobilized artificial membrane (IAMs) chromatographic columns have been shown to be a very efficient way of assessing lipophilic behavior of molecules useful for biomembrane absorption studies (Lepont and Poole, 2002). These stationary phases, containing a monolayers of phosphatidylcholine immobilized on a silica support, are thought to mimic very closely a membrane bilayer and are used in an HPLC system with a physiological buffer as eluent (Manhold et al, 1996;Lepont and Poole, 2002;Liu et al, 1995;Barbato et al, 1996a,b;Ducarme et al, 1998;Caldwell et al, 1998;Norinder and Osterberg, 2000;Kepczynska et al, 2000). In particular, the IAM.PC.DD2, column employed in this work consists of diacyl double chain ester phosphatidylcholine ligands surface-bonded to an aminopropylsiloxane-bonded silica substrate and end capped by mixed propionic and decanoic alkylamide groups.…”