关键词: 医疗器械, 气相色谱法, 环氧乙烷, 2-氯乙醇, 乙二醇

Abstract:

A gas chromatography-based method was developed for the simultaneous and rapid determination of ethylene oxide (EO), 2-chloroethanol (ECH), and ethylene glycol (EG) residues in medical devices after EO sterilization. A sample weighing 2.5 g was added with 5 mL of ethanol as the extraction medium, and the residual substances in the sample were extracted at 40 ℃ for 4 h. The samples were separated on a DB-WAX capillary column (30 m×0.53 mm×1.0 μm) and determined using a hydrogen flame ionization detector. The temperature was maintained at 40 ℃ for 5 min, increased to 120 ℃ at a rate of 40 ℃/min, held for 5 min, and then increased to 200 ℃ at a rate of 6 ℃/min, held for 2 min. The flow rate of the nitrogen gas was 3 mL/min. The split ratio was 5∶1. The inlet and detector temperatures were 200 and 300 ℃, respectively. The changes in the chromatographic peak areas over time (0.5-10 h) under different temperatures (20, 30, 40, and 50 ℃) were investigated, and the optimal extraction condition was determined to be 40 ℃ for 4 h. In the experiments, quantification was performed using an external standard method. EO, ECH, and EG exhibited good peak shapes and separation effects as well as good linearity within their respective ranges. The linear correlation coefficients for EO, ECH, and EG were greater than 0.99. The limits of detection (LODs) for EO, ECH, and EG were in the range of 0.10-0.40 μg/g, and the limits of quantification (LOQs) were in the range of 0.30-1.20 μg/g. The average recoveries under different spiked levels were in the range of 91.08%-116.08%, and the relative standard deviations (n=6) were in the range of 0.56%-8.45%. EO, ECH, and EG residues were found to exist at different levels in the medical devices tested. In particular, disposable infusion sets must be paid careful attention. ECH and EG were not detected in disposable sterile medical devices made of non-polyvinyl chloride materials, which may be due to the fact that the products themselves did not contain chloride ions, they were not exposed to chlorine-containing substances during their production, sterilization, storage, transportation, use, etc. This study established a method to detect EO residues in disposable medical devices, and has the advantages of simple operation, excellent specificity, accurate quantification, and good reproducibility. It can simultaneously detect three residual substances in medical devices while meeting the actual detection requirements for EO, ECH, and EG residues. The method can be used to scientifically and effectively evaluate the risk of EO residues in single-use medical devices sterilized with EO, and will be helpful for improving the quality of medical devices, ensuring the safety of device use, and providing a reference for regulatory supervision and testing.

Key words: medical devices, gas chromatography (GC), ethylene oxide (EO), 2-chloroethanol (ECH), ethylene glycol (EG)