The aim of this research was to explore the role of various reactive species (*DOM, •OH and 1O2) during indirect photodegradation of pharmaceuticals commonly found in wastewater. Additionally, this work studied the effect of particulate organic matter (POM) obtained from wastewater and natural water sources on the photodegradation of pharmaceuticals. Photodegradation of pharmaceuticals may result in the formation of several degradation products, which require computational techniques to identify the active sites. Thus, Density Functional Theory (DFT) based calculations together with UHPLC-MS/MS analysis were used to obtain insights on the active sites participating in the phototransformation processes of the selected pharmaceuticals. Mechanistic studies concerning these aspects are lacking in the literature.