Development of the headspace gas chromatography–tandem mass spectrometry method for ethylene oxide and ethylene chlorohydrin residue in medical devices

Abstract

Rationale

Ethylene oxide (EO) sterilization is commonly employed for the sterilization of medical devices and has a very high market share. However, EO and its metabolite ethylene chlorohydrin (ECH) are toxic to humans. In compliance with the classification and residue limits of medical devices defined by ISO 10993-7, our study established two extraction methods for the testing of EO and ECH.

Methods

The first method involves simulated-use extraction using water as the extraction solvent. While the second, exhaustive extraction, directly extracts sample through headspace sampling analysis. Gas chromatography–tandem mass spectrometry in multiple reaction monitoring mode was utilized, requiring only 16 min. Then, the developed method was applied to assess 10 commercially available medical devices sterilized by EO.

Results

In simulated-use extraction, calibration curves were evaluated in the range of 1–100 and 5–500 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 85.0% to 95.2% and from 94.8% to 102.4%. In exhaustive extraction, calibration curves spanned 0.5–50 and 2–200 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 101.6% to 102.1% for EO and from 98.1% to 102.2% for ECH. After analysis of the 10 commercially available medical devices, two cotton swabs were found to have ECH of 35.1 and 28.4 μg per device, and four medical devices were found to have EO with concentration below the limit of quantification. Meanwhile, we found that the EO internal standard (propylene oxide) recommended by ISO 10993-7 had interference problems with other similar substances and was not suitable as an internal standard for EO.

Conclusions

This study offers a sensitive and straightforward analytical approach to EO and ECH residues in a variety of medical devices. In addition, the results show that the EO or ECH content of these types of medical devices in our study falls below the regulatory limits, therefore instilling confidence among consumers regarding their safe use.