Determination of Ethylene Glycol and Diethylene Glycol in a Sorbitol Solution

Importance of the Topic

A wide range of pharmaceutical and personal care products—including medicinal syrups, toothpaste, and mouthwash—rely on liquid excipients such as sorbitol, glycerin, and propylene glycol. Contamination of these materials with ethylene glycol (EG) or diethylene glycol (DEG) poses significant health risks, causing systemic intoxication, acidosis, multiorgan failure, and fatalities. Regulatory bodies such as the U.S. FDA and USP have set stringent limits (0.1% w/w) for EG and DEG in excipient solutions, underscoring the need for accurate, confirmatory analytical methods.

Study Objectives and Overview

The present work describes two complementary ion chromatography methods with pulsed amperometric detection (IC-PAD) designed to detect and quantify 0.1% (w/w) EG and DEG in sorbitol solutions. Leveraging the Dionex ICS-3000 dual-pump system, the study implements sequential operation of:

• Method 1: High-performance anion-exchange chromatography (HPAE) with NaOH eluent and Au/PTFE electrode for EG.
• Method 2: Mixed-mode ion-exclusion/cation-exchange separation with methanesulfonic acid (MSA) eluent and Pt electrode for DEG.

Methodology and Instrumentation

Instrumentation:

• Dionex ICS-3000 Ion Chromatography system with dual-gradient pump, autosampler with diverter valve, and ED detector.
• CarboPac MA1 Guard (4×50 mm) and Analytical (4×250 mm) columns for EG separation.
• IonPac ICE-AS1 Guard (4×50 mm) and CS14 Analytical (2×250 mm) columns for DEG separation.
• Pulsed amperometric detection using disposable Au/PTFE (EG) and Pt (DEG) working electrodes.

Key experimental conditions:

• Method 1: 200 mM NaOH gradient (40–100%), 0.4 mL/min, 30 °C, four-potential carbohydrate waveform.
• Method 2: 100 mM MSA isocratic, 0.2 mL/min, 30 °C, glycol waveform.

Main Results and Discussion

Method 1 (EG):

• Baseline separation of EG from sorbitol with a run time of 60 min.
• Limit of detection (LOD): 0.25 µg/mL; limit of quantification (LOQ): 0.85 µg/mL.
• Linear calibration range: 1.3–10 µg/mL (r² = 0.9991).
• Spike recovery in 1.3 mg/mL sorbitol (40× dilution): 106%, with retention time and area RSDs < 0.2% and < 3%, respectively.

Method 2 (DEG):

• Efficient resolution of DEG from sorbitol and propylene glycol in 17 min.
• LOD: 3.1 µg/mL; LOQ: 10 µg/mL.
• Linear range: 0.013–0.10 mg/mL (r² = 0.9993).
• Spike recovery in 13 mg/mL sorbitol (4× dilution): 107%, with retention time and area RSDs < 0.3% and < 4%, respectively.

Benefits and Practical Applications

The sequential IC-PAD methods offer direct, sensitive confirmation of toxic glycols at regulatory limits in excipient solutions. They support pharmaceutical quality control by:

• Meeting updated USP 32 NF 27 monograph requirements.
• Minimizing false positives through robust separation and dual detection waveforms.
• Providing reliable quantification in complex sugar matrices.

Future Trends and Opportunities

Ongoing developments may include:

• Automation and high-throughput integration to accelerate sample turnaround.
• Extension of methods to other excipient and beverage matrices.
• Hybrid approaches combining rapid screening (e.g., spectroscopy) with confirmatory IC-PAD.

Conclusion

Two complementary IC-PAD workflows have been validated for determination of 0.1% EG and DEG in sorbitol solutions, achieving regulatory compliance, high sensitivity, and precise quantification.

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