Quantitative determination of residual 1,4-dioxane in three-dimensional printed bone scaffold

Li, Ling; Long, Jing; Li, Long; Cao, Huijuan; Tang, Tingting; Xi, Xinghua; Qin, Ling; Lai, Yuxiao; Wang, Xinluan

According to Chinese Pharmacopoeia 2015 Edition guideline 9101 [26] , accuracy can be evaluated with spiking recovery experiments. Matrix blank can be used to evaluate recovery as described in the guideline. In our sample preparation process, 0.3 g scaffold was dissolved with 4 mL DMF. According to Chinese Pharmacopoeia [26] , International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use [27] , and United States Pharmacopoeia [28] , 1,4-dioxane in the products should be no more than 380 ppm. We convert the concentration of 1,4-dioxane in 0.3 g scaffold (i.e. 380 ppm) into the concentration in 4 mL DMF according to the following formula: 380 ppm  weight of the scaffold (0.3 g)/the weight of DMF Z 380 ppm  0.3g/(volume  density) of DMFZ 380 ppm  0.3g/(4 mL  0.9487 g/L) Z 30 ppm. This means the concentration of 1,4-dioxane in 0.3 g scaffold in 4 mL DMF should be less than 30 ppm. So, 20 ppm, 25 ppm, and 30 ppm of 1,4-dioxane standard solutions were prepared with matrix blank scaffolds in DMF; triplicate samples of each concentration were prepared. The recovery was calculated as follows: (actual concentration/ theoretical concentration)  100%.