Organic Impurities in Ethanol for Alcohol-Based Hand Sanitizer Products

Significance of Topic

The global COVID-19 pandemic has driven unprecedented demand for alcohol-based hand sanitizers. Ethanol and isopropanol used as active ingredients can harbor organic impurities introduced during fermentation or chemical synthesis. Regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the United States Pharmacopeia (USP) mandate strict limits on key contaminants to ensure product safety and efficacy. Reliable analytical methods are therefore essential for routine quality control in pharmaceutical, industrial, and consumer applications.

Study Objectives and Overview

This work evaluates a gas chromatographic method for quantifying organic impurities in high-purity ethanol intended for hand sanitizer production. The study compares the USP monograph list of four regulated impurities with the expanded FDA guidance that includes an additional eight critical compounds. A Shimadzu Nexis GC-2030 system is employed to screen 12 target analytes plus related volatiles, assessing chromatographic separation, calibration linearity, detection limits, and repeatability under both helium and hydrogen carrier gases.

Methodology and Used Instrumentation

A split injection gas chromatograph was configured to meet USP monograph conditions and adapted for FDA guidance analysis. Key parameters and hardware included:

• GC System: Shimadzu Nexis GC-2030 with split/splitless injector, flame ionization detector (FID), and AOC-20 Plus autosampler
• Column: ZB-624 capillary (30 m × 0.32 mm ID, 1.8 μm film thickness)
• Carrier Gas: Helium or hydrogen at a constant linear velocity of 35 cm/s
• Oven Temperature Program: 40 °C hold, ramp 10 °C/min to 240 °C, final hold 10 min
• Injector/FID Temperatures: 200 °C and 280 °C respectively, with optimized gas flows
• Calibration Standards: Multi-level mixes (10–100 ppm) from Bion Sciences, plus custom USP and FDA mixtures

Careful selection of inlet liner (Restek Topaz with wool) and column ensured adequate peak shapes and resolution between critical pairs (acetaldehyde/methanol). Data acquisition and processing utilized LabSolutions LCGC software.

Main Results and Discussion

Chromatographic separation achieved baseline resolution for all 12 target impurities under both carrier gases. Hydrogen delivered slightly higher efficiency (resolution R>1.7) compared to helium (R>1.5) at the specified linear velocity, in agreement with Van Deemter theory.

Calibration employed five-point linear regression (R2>0.998) for most analytes; methanol and benzene required extended calibration ranges to encompass regulatory limits. Benzene detection at the USP limit (2 µL/L) showed signal-to-noise ratios above 11 (up to 17 with stabilized conditions), indicating a practical detection limit near 0.6 µL/L.

Repeatability tests on denatured alcohol demonstrated relative standard deviations below 5.5% for major and minor impurities, except methanol (13.4% RSD) at sub-µL/L levels outside the calibrated range. All measured concentrations fell well under USP and FDA maximum allowable levels.

Benefits and Practical Applications

• Comprehensive screening of USP and FDA impurity lists in a single run
• High resolution and sensitivity for critical analytes such as acetaldehyde, methanol, acetal, and benzene
• Validated linearity and low detection limits compatible with regulatory thresholds
• Use of hydrogen carrier gas reduces operating costs and improves chromatographic efficiency
• Integrated hydrogen sensor and optional gas selector enhance safety during extended analysis

These capabilities support quality assurance in hand sanitizer manufacturing, ethanol production, and related pharmaceutical and industrial processes.

Future Trends and Opportunities

Advances may include automated carrier-gas switching to inert gases during idle periods, further minimizing column oxidation and safety risks. Emerging detector technologies (e.g., micro-FID, photoionization detectors) could broaden sensitivity to trace contaminants. Integration with high-throughput autosamplers and data analytics will accelerate compliance testing and real-time monitoring of production streams. Broader method adaptation may target diverse matrices such as biological fluids or environmental samples.

Conclusion

The Shimadzu Nexis GC-2030 platform, configured with a ZB-624 column and optimized inlet liner, delivers robust analysis of organic impurities in ethanol for hand sanitizer applications. Hydrogen carrier gas offers cost and performance advantages over helium, while achieving regulatory compliance for both USP and FDA requirements. The method exhibits excellent separation, sensitivity, linearity, and repeatability, making it a reliable tool for routine quality control.

Reference

• U.S. Food and Drug Administration. Policy for Temporary Compounding of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency, 2020.
• U.S. Food and Drug Administration. Temporary Policy for Manufacture of Alcohol for Incorporation into Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19), 2021.
• The United States Pharmacopeia Convention. USP Monograph: Alcohol, 2015.
• U.S. Food and Drug Administration. Direct Injection Gas Chromatography Mass Spectrometry (GC-MS) Method for the Detection of Listed Impurities in Hand Sanitizers, 2020.