Interactions of a lyophilized peptide with water and excipients in a solid matrix were explored using photolytic labeling. A model peptide "KLQ" (Ac-QELHKLQ-NHCH) was covalently labeled with NHS-diazirine (succinimidyl 4，4'-azipentanoate)， and the labeled peptide (KLQ-SDA) was formulated and exposed to UV light in both solution and lyophilized solids. Solid samples contained the following excipients at a 1:400 molar ratio: sucrose， trehalose， mannitol， histidine， or arginine. Prior to UV exposure， the lyophilized solids were exposed to various relative humidity (RH) environments (8， 13， 33， 45， and 78%)， and the resulting solid moisture content (Karl Fischer titration) and glass transition temperature ( T; differential scanning calorimetry， DSC) were measured. To initiate photolytic labeling， solution and solid samples were exposed to UV light at 365 nm for 30 min. Photolytic-labeling products were quantified using reversed-phase high-performance liquid chromatography (rp-HPLC) and mass spectrometry (MS). In lyophilized solids， studies excluding oxygen and using HO confirmed that the source of oxygen in KLQ adducts with a mass increase of 18 amu are attributable to reaction with water， while those with a mass increase of 16 amu are not attributable to reaction with either water or molecular oxygen. In solids containing sucrose or trehalose， peptide-excipient adducts decreased with increasing solid moisture content， while peptide-water adducts increased only at lower RH exposure and then plateaued， in partial agreement with the water replacement hypothesis.