Screening of Ethylene Glycol and Diethylene Glycol in Medicinal Syrup by GCMS with FASST mode (Part 1 – as per Indonesian BPOM Method)

Importance of the Topic

The accidental contamination of medicinal syrups with ethylene glycol (EG) and diethylene glycol (DEG) has caused numerous fatal poisonings worldwide, notably in Indonesia and Gambia. Reliable and rapid screening methods are essential to prevent further health crises by ensuring pharmaceutical safety and regulatory compliance.

Objectives and Study Overview

This application note demonstrates the use of Shimadzu GCMS-QP2020 NX coupled with the Fast Automated Scan/SIM Type (FASST) mode to simultaneously identify and quantify trace EG and DEG levels in medicinal syrups, following guidelines from the Indonesian BPOM method. The study aims to establish method performance, including sensitivity, precision, linearity, and recovery, in both control and commercial samples.

Methods and Instrumentation

Sample Preparation:

• Calibration standards (6–14 ppm EG, 12–28 ppm DEG) prepared from 1000 ppm stocks in methanol.
• Blank syrup diluted (10 mL syrup + 90 mL MeOH), sonicated, filtered, and spiked at LOQ levels.
• Commercial samples (Sample A, Sample B) diluted 1:10 with methanol, sonicated, and filtered.

Instrumentation:

• Shimadzu GCMS-QP2020 NX with AOC-20i+s Plus autosampler.
• SH-PolarWax capillary column (30 m × 0.25 mm I.D., 0.25 µm film, with 5 m guard).
• Carrier gas: helium, constant flow 0.65 mL/min, split injection (20:1), injection volume 1 µL.
• Oven program: 100 °C (1 min) → 130 °C @10 °C/min (7 min) → 240 °C @20 °C/min (3 min) → 250 °C @20 °C/min (3 min).
• Ion source 230 °C, interface 240 °C, acquisition in FASST (Scan m/z 29–400, Q3 Scan 0.2 s, SIM 0.1 s).

Main Results and Discussion

Linearity and Sensitivity:

• Calibration curves for EG and DEG showed R² ≥ 0.9985 over the tested ranges.
• Limits of quantification established at 6 ppm for EG and 12 ppm for DEG, with S/N > 200.

Precision and Recovery:

• Intra-day repeatability (n=10): EG %RSD ≈ 1.24%, DEG %RSD ≈ 1.77%.
• Recoveries in blank syrup spiked at LOQ: EG 118–123%, DEG 103–109%.
• Commercial samples: Sample A contained 7.18 ppm EG (no DEG), Sample B contained 10.20 ppm EG and trace DEG (< LOQ).
• Intermediate precision: Sample A EG %RSD ≈ 2.22%; Sample B EG %RSD ≈ 3.92%, DEG %RSD ≈ 54.8% (below LOQ variability).
• Matrix effects led to recoveries of 79–118% for EG and 115–125% for DEG in spiked commercial samples.

FASST Advantages:

• Simultaneous acquisition of Scan and SIM data in one run.
• High specificity: scan data identified co-eluting propylene glycol interferences.
• Enhanced robustness with guard column and high split ratio to handle complex syrup matrices.

Benefits and Practical Applications

This method enables rapid, sensitive screening of EG and DEG in a variety of syrup formulations with minimal sample preparation, making it suitable for high-throughput laboratories, regulatory inspectors, and quality control teams seeking early detection of toxic contaminants.

Future Trends and Potential Applications

• Development of matrix-matched calibration to mitigate matrix effects and improve quantitative accuracy for pharmaceutical QA/QC.
• Integration of automated sample handling and data processing workflows for higher throughput.
• Expansion to other polar contaminants using tailored column chemistries or tandem MS for enhanced selectivity.
• Application of this approach to related formulations such as elixirs, suspensions, or veterinary syrups.

Conclusion

Shimadzu GCMS-QP2020 NX operating in FASST mode demonstrated excellent speed, sensitivity, and reproducibility for simultaneous EG and DEG screening in medicinal syrups. While minimal sample preparation enables rapid testing across diverse matrices, matrix effects may limit quantitative accuracy, underscoring the need for further refinement with matrix-matched standards in follow-up studies.

Reference

1. Barr DB, et al. J. Anal. Toxicol. 2007;31:209–303.
2. Metode Analysis Uji Cemaran Etilen Glikol (EG) dan Dietilen Glikol, BPOM, 2022.
3. Indonesia child deaths blamed on syrup medicines rise to 195, Channel NewsAsia.
4. Indonesia bans cough syrup material linked to Gambia child deaths, Channel NewsAsia.