Estimation of Ethylene Glycol and Diethylene Glycol in Propylene Glycol, Glycerin, and Syrup Samples with the Agilent 8890 GC

Importance of the Topic

Propylene glycol and glycerin are widely used as excipients in pharmaceutical formulations to improve solubility and stability of active ingredients. However, contamination with ethylene glycol (EG) and diethylene glycol (DEG) can pose serious health risks. Regulatory monographs such as the USP set a strict limit of 0.10% for these impurities. Reliable analytical methods are therefore essential to ensure patient safety and regulatory compliance.

Objectives and Study Overview

This study presents the development and validation of a gas chromatographic method using the Agilent 8890 GC equipped with a flame ionization detector (FID) for the identification and quantification of EG and DEG in propylene glycol, glycerin, and syrup samples. The goals include establishing method sensitivity (limit of quantitation at 200 µg/mL), linearity, accuracy, and precision in accordance with pharmacopeial requirements.

Methodology and Instrumentation

Samples were prepared by weighing a defined amount of matrix, adding methanol and 1,3-propanediol as an internal standard, and diluting to volume. Key instrument parameters:

• Gas chromatograph: Agilent 8890 GC with FID
• Column: Agilent J&W DB-624, 30 m × 0.53 mm × 3.00 µm
• Injection: split mode 10:1, volume 0.5 µL, inlet temperature 250 °C
• Carrier gas: helium at 2.5 mL/min
• Oven program: 70 °C (1 min), ramp 6 °C/min to 150 °C (3 min), ramp 25 °C/min to 245 °C (12 min)
• FID conditions: detector at 250 °C, hydrogen 40 mL/min, air 300 mL/min, nitrogen makeup 25 mL/min

Results and Discussion

Calibration curves for EG and DEG over 10–500 µg/mL exhibited excellent linearity (r2 = 0.997 and 0.998, respectively). Repeatability of retention times and peak areas showed RSDs below 0.04% and 3.2%. Spike recovery experiments in propylene glycol, glycerin, and syrup at 200 and 500 µg/mL yielded recoveries between 86% and 122% with RSDs below 3%. Chromatograms confirmed clear resolution of analytes from matrix interferences, and no EG or DEG peaks were detected in unspiked syrup samples.

Benefits and Practical Applications

• Suitable for routine quality control in pharmaceutical production, processing, and commercial testing
• Compliance with USP and other pharmacopeial standards
• High sensitivity and accuracy ensure reliable detection at regulatory limits
• Applicable to a variety of matrices, including excipients and finished syrups

Future Trends and Opportunities

• Integration of mass spectrometric detection for enhanced specificity
• Automation of sample preparation to improve throughput
• Extension of the method to additional excipients and dosage forms
• Implementation of data analytics for method optimization and trend monitoring

Conclusion

The validated GC-FID method on the Agilent 8890 platform offers a robust, sensitive, and precise approach for quantifying EG and DEG in propylene glycol, glycerin, and syrup samples. With proven spike recoveries and repeatability, it supports adherence to safety regulations and routine pharmaceutical quality assurance.

References

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3. U.S. Department of Health and Human Services FDA CDER. Testing of Glycerin, Propylene Glycol, and other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol: Guidance for Industry. 2023.
4. Pharmacopeia CN. USP Method for Glycerol Analysis. 2023.
5. Eccles R. What is the Role of Over 100 Excipients in Over the Counter Cough Medicines? Lung. 2020;198(5):727–734.