A phenyl ether-based drug substance exhibits photochemical degradation in citrate buffers with both ultraviolet (300-450 nm range) and visible light (380-700 nm range) exposure, even though the drug molecule itself is non-light absorbing at wavelengths > 300 nm. The major contributors to the observed photosensitivity are the citrate buffer, parts per billion (ppb) levels of iron, oxygen, and light exposure level. Although a primary phenol photodegradate is generated, there are at least eight other species formed as well. The molecular weights and abundance of these species suggest that the product distribution is generated by the reaction of hydroxyl radicals with the drug substance. The generation of the primary photodegradate is linearly proportional to the light exposure amount for a fixed concentration of iron present in the formulation. Conversely, the amount of photodegradation is also nearly linear with iron concentration (through 200 ppb levels) for a fixed amount of light exposure. The proposed mechanism for the photochemical generation of hydroxyl radicals has precedence in the literature for similar combinations of iron, oxygen, carboxylate buffers, and light. Since the buffer salt and oxygen molecular equivalents in the product are significantly higher than the ppb levels of iron employed and more difficult to remove, the control of the extent of photodegradation largely rests on the control of trace levels of iron in the formulated product and control of light exposure. Exposure of drug solutions to a series of transition metals clearly indicates that iron is the key transition metal involved in the observed photochemistry. At manufacture, the primary source of iron is the raw materials (water, drug or excipients) used in the formulation. The level of iron for product stored in glass increases with sample age and can be attributed to iron leaching from borosilicate glass vials. Consideration of adequate light control during the manufacturing and packaging processes will be discussed and can only be defined as a function of the amount of iron present at the time of manufacture in the formulation. The generality of this chemistry to other drug candidates and in the presence of other common buffers will also be discussed.