The aim of the present investigation was to develop a method to predict blood-brain barrier permeability using a group of model compounds with an in vitro UV spectroscopy method. There are many prediction models reported in journals, but none are yet able to accurately and precisely predict permeation to facilitate the replacement of animal testing. An analytical method was developed using a group of model compounds, namely acetaminophen, ibuprofen, aceclofenac, metronidazole, metformin hydrochloride and norfloxacin. Subsequently, a solubilisation ratio (SR) for the compounds was calculated in the presence of two surfactants (Tween 80 and SDS). Data was used to determine if a correlation could be seen between the SR values calculated and literature blood-brain barrier permeability for the six model compounds. Correlation results (R2 values) were found for Tween 80 and SDS to be lower than hoped at only 0.418 and 0.499 respectively. However, it can be concluded that the present study required more investigation for establishing this technique and it may only be a suitable methodology with further work.