Midazolam, a potent anxiolytic drug with sedative properties, is susceptible to degradation by both light and hydrolysis in aqueous solution. When formulated as an intranasal product it was found to be effective in achieving seizure control in epileptic patients. In order to deliver an adequate therapeutic dose to a patient, a nasal formulation requires the concentration of midazolam to be higher than its? aqueous solubility. One way to increase midazolam solubility to a therapeutic concentration, is complexation with randomly methylated-?-cyclodextrin. Thus, it is important to determine how complexation with cyclodextrin affects the rate of degradation and type of midazolam degradants that are formed. We have found that complexation with cyclodextrin decreases its photostability. More importantly, the degradation profile for midazolam is significantly altered when it is complexed with randomly methylated-?-cyclodextrin, what we partly confirmed in our previous work.1 By continuing our study we have found that degradation products, not observed on the photodegradation of uncomplexed midazolam are observed in significant quantities when it is complexed with randomly methylated-?-cyclodextrin. The decreased photostability was accompanied by the appearance of two new degradation products, an intermediate structure and a dimer. Photoproduct formation followed the same pattern as in the forced degradation studies, further confirming the presence of an intermediate. The production of these new photodegradants, characterized with their MS spectra, as well as proposed degradation mechanism of midazolam is discussed.