Analysis of Ethylene Glycol and Diethylene Glycol in Propylene Glycol

Importance of the Topic

Propylene glycol is a common pharmaceutical excipient and food additive due to its solvent properties and safety profile. Trace impurities such as ethylene glycol and diethylene glycol are toxic even at low concentrations, making their reliable detection essential for product quality and patient safety.

Objectives and Study Overview

This study presents a gas chromatographic method aligned with Supplement II of the Japanese Pharmacopoeia 16th Edition to separate and quantify ethylene glycol, propylene glycol, and diethylene glycol. The goals include:

• Verification of system suitability and performance criteria.
• Assessment of repeatability for ethylene glycol and diethylene glycol peak areas.
• Application of the method to commercial propylene glycol samples to confirm impurity levels.

Methodology and Instrumentation

The analysis was conducted on a GC-2010 Plus AF system equipped with an AOC-20i autosampler. A capillary Rtx-1701 column (30 m × 0.32 mm i.d., 1.0 μm) was used under the following conditions:

• Injection temperature: 220 °C; detector temperature: 250 °C.
• Column program: 100 °C hold, ramp 7.5 °C/min to 220 °C, hold 4 min.
• Carrier gas: helium at 38 cm/sec; split ratio: 1:20; injection volume: 1 μL.

System suitability involved mixing 50 mg each of ethylene glycol, propylene glycol, and diethylene glycol in 100 mL methanol and verifying resolution criteria: ≥ 5 between ethylene/propylene glycols and ≥ 50 between propylene/diethylene glycols. Repeatability testing used six injections of a standard solution (0.1% w/v each for ethylene and diethylene glycols, 5% w/v propylene glycol) with target RSD ≤ 10%.

Main Results and Discussion

• System suitability chromatogram showed resolutions of 6.11 (ethylene/propylene) and 64.4 (propylene/diethylene), exceeding pharmacopoeial requirements.
• Repeatability results yielded RSDs of 0.67% for ethylene glycol and 0.78% for diethylene glycol, well under the 10% threshold.
• Sample analysis of commercial propylene glycol (50 g/L) displayed no significant peaks (> 0.1% area) for the two impurities, and total impurity area stayed below 1.0%.

Benefits and Practical Applications

This validated GC method ensures compliance with Japanese Pharmacopoeia standards, providing laboratories with a reliable approach for routine quality control of propylene glycol and for safeguarding consumer health.

Future Trends and Opportunities

Anticipated developments include faster temperature gradients or shorter columns to reduce run time, implementation of mass spectrometric detection for enhanced selectivity, and automation for high-throughput impurity screenings. Continuous method refinement will support broader regulatory harmonization and real-time monitoring in production environments.

Conclusion

The described gas chromatographic procedure offers robust separation, precise quantification, and repeatable performance for ethylene glycol and diethylene glycol impurities in propylene glycol, fulfilling pharmacopoeial requirements and strengthening product safety assurance.

Reference

• Ministry of Health, Labour and Welfare Notification No. 47, Supplement II to Japanese Pharmacopoeia 16th Edition (2011).
• Shimadzu Corporation. Application News G282: Analysis of Ethylene Glycol and Diethylene Glycol in Propylene Glycol, First Edition, Mar. 2015.