Acetaminophen (AAP) is a popular antipyretic drug, and its combination with opioid analgesics is used for treatment of chronic arthritis. Opioid analgesics cause constipation as a side effect, which is generally relieved by use of a laxative like MgO. Since a discoloration was found in a mixture of acetaminophen granules (AAP-G) and MgO fine granules (MgO-FG) preserved for 90 days, we investigated the discoloration-causing substance. We clarified that AAP and MgO are responsible for the discoloration, according to the temporal changes of each component in AAP-G and MgO-FG. We obtained the reflected absorption spectra of AAP and the AAP/MgO mixture using the integrating sphere in solid state. The integrating sphere is used to measure suspensions and solid samples by capturing the light irradiated on the sample as homogeneous scattered light inside the sphere. The spectra of AAP and AAP/MgO (preserved for 77 days) showed a new reflected absorption peak at 395 nm and 451 nm, respectively. The spectrum of the AAP/MgO mixture showed a peak similar to the 467 nm peak obtained by peak separation of the reflection spectrum of AAP upon heating oxidation. Therefore, this suggests that progress of the oxidation reaction occurs. However, the reflected absorption peak at 395 nm for AAP alone suggested the photo-Fries rearrangement reaction. In the present study, the measurement of the AAP/MgO mixture using the integrating sphere clarified two reactions occurring on the solid surface. The integrating sphere is considered a useful technique for analyzing solid samples like powders and granules.