Organic Impurities in Ethanol for Alcohol-Based Hand Sanitizer Products

Significance of the Topic

The COVID-19 pandemic triggered a massive surge in demand for alcohol-based hand sanitizers. Ensuring consumer safety requires sensitive and reliable detection of trace organic contaminants in ethanol, which can arise during production. Regulatory bodies such as the United States Pharmacopeia (USP) and the U.S. Food and Drug Administration (FDA) have established impurity lists and maximum allowable concentrations, making robust analytical methods critical for quality control.

Aims and Study Overview

This application note evaluates a gas chromatography–flame ionization detection (GC-FID) method for screening an extended panel of organic impurities in ethanol used for hand sanitizers. The study follows the USP monograph for alcohol and the expanded FDA guidance, covering 12 regulated compounds and additional analytes. Key objectives include achieving regulatory-level separation, establishing calibration performance, determining detection limits, and assessing method repeatability.

Methodology and Instrumentation

This work employs a Shimadzu Nexis GC-2030 system with split/splitless injector, flame ionization detector, and AOC-20 Plus autosampler. A Restek ZB-624 capillary column (30 m × 0.32 mm × 1.8 µm) was selected after comparative testing against ZB-624 Plus and other G43 phases. Optimal conditions include split injection (1:20), 1 µL volume, helium or hydrogen carrier gas at a constant linear velocity of 35 cm/s, and a temperature program from 40 °C (12 min) to 240 °C at 10 °C/min.

• Shimadzu GC-2030 with SPL injector, FID, AOC-20 Plus autosampler
• ZB-624 column, 30 m × 0.32 mm × 1.8 µm
• Carrier gas: He or H₂, 35 cm/s constant linear velocity
• Injection: split 1:20, 1.0 µL, inlet 200 °C
• Oven program: 40 °C (12 min) → 240 °C at 10 °C/min (10 min hold)
• FID: 280 °C, H₂ 32 mL/min, air 200 mL/min, N₂ makeup 24 mL/min

Main Results and Discussion

All 20 target compounds, spanning acetaldehyde, methanol, benzene, acetal, level 2 impurities, solvents (acetone, acetonitrile), and denaturants, were baseline resolved. Hydrogen improved resolution between acetaldehyde and methanol (R > 1.7) compared to helium (R > 1.5). Retention times differed by only a few seconds between gases. Calibration was linear (r² > 0.998) across five levels (10–100 ppm), with six-point curves for methanol (10–200 µL/L) and benzene (2–90 µL/L). Benzene’s detection limit was determined at ~0.6 µL/L (S/N > 11). Repeatability in denatured alcohol (n = 10) yielded RSD < 5.5% for most compounds; methanol exhibited 13.4% RSD at sub-µL/L levels.

Benefits and Practical Applications

• Meets USP and FDA impurity criteria for alcohol-based sanitizers
• Comprehensive screening of regulated and supplemental analytes
• Hydrogen carrier gas offers cost savings and higher chromatographic efficiency
• Integrated hydrogen sensor enhances operational safety
• Suitable for high-throughput QA/QC laboratories

Future Trends and Applications

Advances may include coupling to mass spectrometric detection for enhanced specificity, integrating automated gas-switching valves for inert post-run column protection, and deploying software-driven data workflows for real-time compliance monitoring. Adaptation to isopropanol-based products and other volatile matrices is also anticipated.

Conclusion

The Shimadzu Nexis GC-2030 with ZB-624 column delivers robust performance in analyzing organic impurities in ethanol, satisfying both USP and FDA requirements. Using hydrogen carrier gas optimizes separation efficiency and cost, while built-in safety features support reliable routine operation.

References

• FDA, Policy for Temporary Compounding of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency, 2020.
• FDA, Temporary Policy for Manufacture of Alcohol for Incorporation into Alcohol-Based Hand Sanitizer Products During the Public Health Emergency, 2021.
• United States Pharmacopeia, Alcohol Monograph, USP Convention, 2015.
• FDA, Direct Injection Gas Chromatography Mass Spectrometry Method for the Detection of Listed Impurities in Hand Sanitizers, 2020.