Evaluation of sphingomyelin, cholester, and phosphatidylcholine-based immobilized artificial membrane liquid chromatography to predict drug penetration across the blood-brain barrier

Abstract

Over the past decades, several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier. So far, in high-performance liquid chromatography, most attention has been paid to micellar liquid chromatography and immobilized artificial membrane (IAM) LC. IAMLC has been described as a viable approach, since the stationary phase emulates the lipid environment of a cell membrane. However, research in IAMLC has almost exclusively been limited to phosphatidylcholine (PC)-based stationary phases, even though PC is only one of the lipids present in cell membranes. In this article, sphingomyelin and cholester stationary phases have been tested for the first time towards their ability to predict drug penetration across the blood-brain barrier. Upon comparison with the PC stationary phase, the sphingomyelin- and cholester-based columns depict similar predictive performance. Combining data from the different stationary phases did not lead to improvements of the models.

Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases

“…The octadecylsilyl (ODS) stationary phase provides a fast approach, but immobilized artificial membranes (IAMs) are more similar to the membranes of eukaryotic cells and therefore better mimic biological systems [10][11][12]. Artificial membranes are more similar to biological systems because they anchor synthetic phosphatidylcholine analogues to silica [13][14][15][16][17][18]. Cholesterol is one of the major components of many eukaryotic membranes and it seems highly likely that cholesterol immobilized on silica would offer similar possibilities.…”

Affinity chromatography: A review of trends and developments over the past 50 years

“…For instance, lipids have been used in immobilized artificial membrane (IAM) chromatography to determine the partition coefficients of drugs for cell membranes [202]. Monolayers of phospholipid analogs such as phosphatidyl choline, sphingomyelin, and choline have all been used as biological ligands in this method [203][204][205]. IAM has been employed for examining drug interactions with immobilized receptors and transporters [206][207][208][209][210].…”

Into the first biomimetic sphingomyelin stationary phase: Suitability in drugs’ biopharmaceutic profiling and block relevance analysis of selectivity

“…datasets Acids and Bases), they were taken from DrugBank (Wishart et al, 2018), except for verapamil, 4-amino benzoic acid, celecoxib, chlorambucil and fexofenadine, whose source was PubChem (Kim et al, 2016). Chromatographic retention data achieved on both IAM.PC and IAM.SPH stationary phases in the same experimental conditions were gathered from (De Vrieze et al, 2014). In vivo data of membrane passage were collected from (Avdeef, 2012), while in vitro PAMPA BBB measurements were used from (Tsinman et al, 2011).…”

“…However, in 2011, a prototype SPH stationary phase for IAM chromatography was synthesized by an ultra-short, solid-phase inspired methodology (Verzele et al, 2012), in which an oxidative release monitoring strategy played an essential role. This prototype was evaluated in a proof-of-concept model for BBB passage (De Vrieze et al, 2014). However, while there is a conspicuous amount of literature aimed at modeling (Taillardat-Bertschinger et al, 2002), and at some extent predicting (Russo et al, 2017a), the retention of chemically diverse solutes on the IAM.PC phases commercially available, no data is available so far with regards to prediction and mechanism elucidation of analytical retention on IAM phases based on SPH.…”