Analysis of Residual Ethylene Oxide in Medical Devices by Gas Chromatography

Importance of the Topic

Ethylene oxide sterilization is widely employed for medical devices due to its effectiveness against microorganisms. However, residual ethylene oxide and its byproducts, ethylene chlorohydrin and ethylene glycol, pose potential health risks and must be monitored to ensure patient safety and regulatory compliance.

Study Objectives and Overview

This study aimed to develop and validate a gas chromatography method for the simultaneous analysis of residual ethylene oxide (EO), ethylene chlorohydrin (ECH), and ethylene glycol (EG) in medical devices. The method was referenced against JIS T 0993-7:2012 and ISO 10993-7:2008 standards to meet international measurement requirements.

Applied Methodology

• Extraction approach: simulated-use or exhaustive extraction using water as solvent.
• Standard solutions: 100 µg/mL EO stock, 500 µg/mL mixed ECH/EG stock; calibration levels prepared at 1, 5, 10, and 25 µg/mL.
• Sample introduction enhancement: 20 mg deactivated glass wool packed into a split glass insert to stabilize peak shape and improve reproducibility.

Used Instrumentation

• Gas chromatograph: Shimadzu Nexis GC-2030 with AOC-20i Plus autosampler.
• Detector: FID-2030 flame ionization detector.
• Analytical column: SH-Stabilwax (30 m × 0.53 mm I.D., 1 µm film).
• Oven program: 60 °C hold for 3 min, ramp 20 °C/min to 200 °C, hold 10 min (20 min total).
• Injection conditions: split mode, 0.5 µL injection volume, split ratio of 3, injector temperature 250 °C.
• Carrier gas: nitrogen at constant linear velocity of 40 cm/s.
• Detector gases: hydrogen 32 mL/min, air 200 mL/min, makeup nitrogen 24 mL/min.

Main Results and Discussion

• Linearity: Correlation coefficients (R²) ≥ 0.9993 for EO, ECH, and EG across 1–25 µg/mL.
• Precision: Peak area RSDs < 1.4% for EO and ECH, < 5.8% for EG at the lowest concentration, satisfying ≤ 5% requirement.
• Resolution: Baseline separation achieved with resolution > 2 between EO and adjacent peaks.
• Tailing factors: ≤ 1.47 for EO, ≤ 1.10 for ECH, ≤ 1.47 for EG, meeting ≤ 1.8 criterion.
• Detection limits: EO ~ 0.11–0.12 µg/mL, ECH ~ 0.14–0.16 µg/mL, EG ~ 0.15–0.29 µg/mL (S/N=3).
• Quantification limits: EO ~ 0.36–0.41 µg/mL, ECH ~ 0.48–0.53 µg/mL, EG ~ 0.48–0.95 µg/mL (S/N=10).

Benefits and Practical Applications

• Simultaneous determination of EO, ECH, and EG reduces analysis time and solvent use compared to separate methods.
• Method fully complies with JIS T 0993-7:2012 and ISO 10993-7:2008 regulatory requirements.
• High reproducibility and sensitivity support routine quality control of sterilized medical devices.
• Simplified workflow enhances laboratory efficiency and data consistency.

Future Trends and Potential Applications

Further development may focus on integrating mass spectrometric detection for improved selectivity, automating sample preparation to increase throughput, and expanding the method to monitor additional sterilization byproducts and diverse medical device materials.

Conclusion

The validated GC-FID method on the Shimadzu Nexis GC-2030 platform provides reliable, reproducible, and compliant analysis of residual EO, ECH, and EG in medical devices, facilitating enhanced quality assurance in sterilization monitoring.

Reference

No specific literature references were provided.