Photocatalysis as a Tool for in Vitro Drug Metabolism Simulation: Multivariate Comparison of Twelve Metal Oxides on a Set of Twenty Model Drugs

Abstract

The constant development in the area of medicinal substances on the market and their subsequent progress in the field of drug analysis has become one of the reasons for the search for alternative, cheaper, and faster methods to determine the metabolism pathways of new molecular entities (NMEs). The simulation of transformation processes using photocatalysis is considered to be one of the promising methods. Although its effectiveness has been proven, the research has so far focused especially on titanium dioxide, while a more accurate comparison of the suitability of different photocatalysts in terms of their use in drug metabolism studies has not been performed. For this purpose, a set of twelve metal oxides was prepared and their photocatalytic efficiency in the direction of drug metabolism mimicking was checked on a model mixture of twenty medicinal substances differing both in chemical structure and pharmacological properties. Incubation with human liver microsomes (HLMs) was used as the reference method. The metabolic profiles obtained with the use of LC-MS analysis were compared using multidimensional chemometric techniques; and the graphic presentation of the results in the form of PCA plot and cluster dendrogram enabled their detailed interpretation and discussion. All tested photocatalysts confirmed their effectiveness. However, the exact outcome of the study indicate advantage of the WO3-assisted photocatalysis over other metal oxides.