Analysis of Ethylene Glycol and Diethylene Glycol in Glycerin, Propylene Glycol and Sorbitol via GC-FID in Accordance with USP Monographs

Significance of the Topic

Glycerin, propylene glycol and sorbitol are widely used excipients in pharmaceutical syrup formulations and their safety is critical to prevent contamination by toxic glycols such as ethylene glycol and diethylene glycol. Incidents of fatal contamination have highlighted the need for robust quality control throughout the supply chain and finished product testing

Objectives and Study Overview

This study aims to establish a rapid and reliable gas chromatography flame ionization detection method in accordance with United States Pharmacopeia monographs for the determination of ethylene glycol and diethylene glycol in raw materials glycerin, propylene glycol and sorbitol. Analytical performance is evaluated using system suitability tests, repeatability, signal to noise ratio and spiked sample recovery

Methodology and Used Instrumentation

The analysis was performed on a Shimadzu GC-2010 Pro gas chromatograph equipped with an AOC-20i+s Plus autosampler and a flame ionization detector supplied by hydrogen from a PEAK Scientific Precision SL 100 generator. Columns used include SH-624 USP G43 phase for glycerin and propylene glycol and SH-1701 USP G46 phase for sorbitol. Key parameters comprised split injection with reduced volume to 0.5 microliter for glycerin and PG, oven temperature ramps tailored to each matrix and FID temperatures set between 250 and 300 °C. Sample and standard preparations followed USP monograph guidelines with diluents and internal standard 2,2,2-trichloroethanol

Main Results and Discussion

System suitability tests demonstrated resolution values well above USP requirements of 1.5, 5 and 30 for the critical peak pairs in glycerin, propylene glycol and sorbitol respectively. Repeatability studies yielded relative standard deviations below 3% and signal to noise ratios exceeding 25 at the limit of quantification of 0.1%. No ethylene glycol or diethylene glycol was detected in unspiked raw material samples confirming compliance with USP limits. Spiked samples containing 0.11% of each glycol returned peak response ratios and areas that surpassed standard values, validating method accuracy and sensitivity

Benefits and Practical Applications

• The method provides fast and robust screening for toxic glycol contaminants in key pharmaceutical raw materials
• Shimadzu GC-2010 Pro combined with AOC-20i+s Plus autosampler delivers high throughput and reproducible results under USP protocols
• Reduced injection volume minimizes risk of backflash and system contamination while maintaining detection reliability
• Workflow supports multi level quality control from raw material release to finished product monitoring

Future Trends and Opportunities

• Integration of automated sample preparation and data processing to enhance laboratory efficiency
• Expansion of method scope to related solvents and potential impurities in pharmaceutical and consumer healthcare matrices
• Development of on site portable GC-FID systems for rapid field screening in supply chain audits
• Adoption of hyphenated techniques such as GC-MS for confirmatory analysis and structural elucidation of unknown impurities

Conclusion

The described GC-FID method reliably quantifies trace levels of ethylene glycol and diethylene glycol in glycerin, propylene glycol and sorbitol complying with USP monograph requirements. High resolution, precision and low detection limits make this approach suitable for routine quality control in pharmaceutical and consumer healthcare industries. Shimadzu GC-2010 Pro with AOC-20i+s Plus ensures robust performance and adaptability for stringent impurity testing needs

References

1. WHO reports on toxic cough syrup incidents and regulatory alerts in Indonesia and Uzbekistan
2. United States Pharmacopeia monographs for glycerin, propylene glycol and sorbitol
3. Shimadzu application news detailing improved GC-MS based impurity screening methods