Abstract: To investgate the structure and source of unknown components in the residual solvent, Fludeoxyglucose ¹⁸F injection was analyzed by GC-MS. The results indicated that the main unknown impurity was trimethylsilanol which came from the degradation of backing material in C18 column during the on-column basic hydrolysis process. The content of trimethylsilanol was determined by GC, and the method validation results met the requirements. The linear range was from 0.003 mg/mL to 1.5 mg/mL, and the correlation coefficient was 0.999 1. The limits for detection and quantitation were 0.001 mg/mL and 0.003 mg/mL respectively. 56 batches of ¹⁸F-FDG samples containing trimethylsilanol were measured, and the concentration of trimethylsilanol was from 0.003 mg/mL to 0.380 mg/mL. The results show that the unknown components in the residual solvent determination are not organic solvent residues. It is suggested that the preparation process should be improved to avoid the impurities from the column packing degradation.