According to the International Conference on Harmonisation (ICH) Q3A (R2) guideline, the identification threshold of an impurity for drug substance with a maximum daily dose of 2 g or less is 0.1% or 1.0 mg whichever is lower. In addition, the Ministry of Food and Drug Safety (MFDS) of Korea requires the submission of a genotoxicity assessment report for any unspecified impurities above the identification threshold. In the photostability test of dexamethasone drug substance at UV 200 watt/m², Vis 1,200,000 lux, two unspecified impurities (i.e. unknown impurity 6 and unknown impurity 10) were detected above the identification level (0.1%). The structures of the impurities were predicted through literature research and identified through LC-MS/MS. According to the LC-MS/MS results, the m/z values of the precursor ion of dexamethasone API and unknown impurity 10 were 392.7 and 333.0, respectively. The literature review confirmed that unknown 10 is a photodegradation product ("androderivative") of betamethasone, which is an epimer of dexamethasone. The precursor ion of unspecified impurity 6 had an m/z value of 409.2, which implies that unknown impurity 6 would be a derivative of dexamethasone with a hydroxyl (-OH) group. Considering that dexamethasone has six positions where the hydroxyl group can be attached, a total of six candidates were selected. The most likely structure of unknown impurity 6 among the candidates was identified based on mass fragment matching and Log P value (partition coefficient). The genotoxicity of the candidates for any unspecified impurities (i.e. unknown 6, unknown 10) that are photodegradation products of dexamethasone was evaluated using the Quantitative Structure Activity Relationship (QSAR) program, and all of the impurities were class 5 compounds with no risk of genotoxicity (ICH M7).