Prediction of the Blood-Brain Barrier Permeability Using RP-18 Thin Layer Chromatography

• Main Authors: Sobańska Anna W., Wanat Karolina, Brzezińska Elżbieta
• Format: Article
• Language: English
• Published: De Gruyter 2019-02-01
• Series: Open Chemistry
• Subjects: rp-18 tlc; qsar; blood-brain barrier; chemometric techniques
• Online Access: https://doi.org/10.1515/chem-2019-0005

The Blood-Brain Barrier (BBB) permeability is an important factor governing a drug’s ability to act upon the Central Nervous System. The measure of the BBB permeability used throughout this study is the log BB (the blood/brain partitioning coefficient) measured in vivo or calculated. Useful yet simple models of the BBB permeability were developed by Stepwise Multiple Regression Analysis based on the chromatographic parameters Rf and Rf/PSA obtained by RP-18 TLC with acetonitrile - pH 7.4 phosphate buffered saline 70:30 (v/v) as mobile phase, combined with descriptors - the number of H-bond donors (HD), the number of H-bond acceptors (HA), energy of the highest occupied molecular orbital – (eH), energy of the lowest unoccupied molecular orbital (eL). The ability of the solutes to cross the BBB has been studied qualitatively using Discriminant Function Analysis. Almost all compounds with the known BB vivo parameter were correctly classified as CNS+/-. The classification functions based on Rf/PSA have been verified using an external group. The results of the chromatographic analysis proposed in this study (RP-18 TLC) are a source of valuable information on the BBB permeability of compounds available even on a very small scale.