ObjectiveTo establish a more accurately method to detect the residue of 1,4-butanediol diglycidyl-ether (BDDE) in the cross-linked sodium hyaluronic gel so as to provide a scientific testing method for the quality control. MethodsThe gas chromatography was used to explore the thermal stability of BDDE, and the residues of BDDE in sodium hyaluronic gel was detected by fluorescence spectrophotometry. The hyaluronidase was added to the BDDE standard solution and the improved fluorescence spectrophotometer was used to detect the BDDE residues in the cross-linked hyaluronic sodium gel. ResultsA good linearity was obtained as y=14.102x+1.103 (R2=0.999 8) for BDDE. BDDE was unstable under high temperature and long storage time. The relevant fluorescence intensity was detected with hyaluronidase solution. After adding hyaluronidase into the BDDE standard solutions, the advanced linearity was obtained as y=14.027x+7.062 (R2=0.999 9). ConclusionFluorescent spectrophotometry is a simple, rapid, and accurate method to analyze BDDE residue of cross-linked sodium hyaluronic gel. Due to the poor thermal stability, all the factors related to temperature must be excluded during the process, including the temperature control of every step. Furthermore, the adding of hyaluronidase in the pre-preparation of cross-linked sodium hyaluronic gel can bring interference. So when using fluorescent spectrophotometry, adjustment must be taken before the calibration curve is preparation.