Quantitative determination of residual 1,4-dioxane in three-dimensional printed bone scaffold.
Quantitative determination of residual 1,4-dioxane in three-dimensional printed bone scaffold.
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三维打印骨支架中1,4-二恶烷残留量的定量测定
DOI：
10.1016/j.jot.2017.06.004
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发表时间：
2018-04
影响因子：
6.6
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Li L;Long J;Li L;Cao H;Tang T;Xi X;Qin L;Lai Y;Wang X
采用三维打印技术制备了一种新型的聚乳酸-羟基乙酸共聚物-磷酸三钙多孔支架材料（PLGA/TCP），用于骨缺损的修复。作为一种毒性较轻的2类溶剂，这种新开发的支架中残留的1，4-二氧六环含量在转化为临床使用时应严格控制。本研究建立了PLGA/TCP复合支架材料中1，4-二氧六环的顶空气相色谱-质谱（HS-GC-MS）定量分析方法。采用基质效应分析优化支架的预处理方法。然后，建立了使用HS-GC-MS检测1，4-二氧六环的程序。在用不同干燥程序定量支架中的1，4-二氧六环之前，还验证了这种新开发的定量方法的准确度、精密度和耐用性。二甲基甲酰胺（DMF）是GC-MS溶解支架的最佳溶剂，具有适当的灵敏度，无基质效应。然后，确定优化的程序为：将支架溶解在DMF中并在90°C下保持40分钟，在HP-5 MS柱上分离，并通过质谱检测。回收率实验得出1，4-二氧六环的回收率为97.9-100.7%。测定1，4-二氧六环的线性范围为1-40 ppm，线性相关系数≥ 0.9999。日内和日间精密度确定为在低于0.68%的相对标准偏差范围内。可通过的干燥程序涉及将支架冻干（-50 °C，50 Pa）2天并在真空（50 Pa）中干燥7天。这是第一个建立的定量方法来测试1，4-二氧杂环己烷在一个新的支架。该方法经验证具有良好的准确度和重现性，符合中国药典2015年版指导原则9101的方法学要求。这种测定新型支架中残留1，4-二氧六环的定量方法是其转化为临床使用的关键技术方法，因为该方法是多孔支架作为骨缺损修复用III类植入医疗器械注册时企业标准中不可缺少的重要文件，用于保证支架的安全性。它还用于优化支架的干燥过程，并在工业化过程中监控支架的质量。该方法为多孔支架或材料中其他溶剂的定量测定提供了参考。
A novel porous scaffold poly (lactide-co-glycolide) and tricalcium phosphate (PLGA/TCP) was developed by three-dimensional printing technology for bone defect repair. As a Class 2 solvent with less severe toxicity, content of residual 1,4-dioxane in this newly developed scaffold should be rigorously controlled when it is translated to clinical use. In this study, a headspace gas chromatography-mass spectrometric (HS-GC-MS) method and related testing protocol were developed for quantitative determination of 1,4-dioxane in the PLGA/TCP composite scaffolds. Matrix effect analysis was used to optimise the pretreatment method of the scaffolds. Then, the procedure for testing 1,4-dioxane using HS-GC-MS was set up. The accuracy, precision, and robustness of this newly developed quantitative method were also validated before quantification of 1,4-dioxane in the scaffolds with different drying procedures. Dimethyl formamide (DMF) was the optimal solvent for dissolving scaffolds for GC-MS with proper sensitivity and without matrix effect. Then, the optimised procedure was determined as: the scaffolds were dissolved in DMF and kept at 90°C for 40 minutes, separated on a HP-5MS column, and detected by mass spectroscopy. Recovery experiments gave 97.9–100.7% recovery for 1,4-dioxane. The linear range for 1,4-dioxane was determined as 1–40 ppm with linear correlation coefficient ≥ 0.9999. Intraday and interday precision was determined as being within relative standard deviation of below 0.68%. The passable drying procedure was related to lyophilising (−50°C, 50 Pa) the scaffolds for 2 days and drying in vacuum (50 Pa) for 7 days. This is the first quantitative method established to test 1,4-dixoane in a novel scaffold. This method was validated with good accuracy and reproducibility, and met the methodological requirements of the Guideline 9101 documented in the Chinese Pharmacopoeia 2015 Edition. This quantitative method for determination of residual 1,4-dioxane in the novel scaffolds is a key technical method during its translation into clinical use because this method is an important and indispensable file in the enterprise standard when the porous scaffold is registered as a Class III implanted medical device for bone defect repair, which is used to guarantee the safety of the scaffolds. It is also applied to optimise the drying process of scaffolds and to monitor the quality of scaffolds in the industrialisation process. Further, this method provides references for other solvents quantitative determination in porous scaffolds or materials.
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影响因子：
1.7
作者：
RASTOGI, SC
通讯作者：
RASTOGI, SC
影响因子：
6.6
作者：
Li Y;Chen SK;Li L;Qin L;Wang XL;Lai YX
通讯作者：
Lai YX
影响因子：
9.7
作者：
Chen, S. -H.;Lei, M.;Qin, L.
通讯作者：
Qin, L.
影响因子：
9.7
作者：
LUNDBERG, I;HOGBERG, J;HOLMBERG, B
通讯作者：
HOLMBERG, B
影响因子：
4
作者：
Xie, Xin-Hui;Wang, Xin-Luan;Qin, Ling
通讯作者：
Qin, Ling