Analysis of Volatile Impurities in Anhydrous Ethanol and Ethanol for Disinfection in Accordance with the Purity Test set by the Pharmacopoeias (JP, USP, EP)

Importance of the Topic

Ethanol is widely used as a disinfectant and pharmaceutical solvent. Ensuring its safety requires stringent monitoring of volatile impurities such as methanol, acetaldehyde, acetal and benzene. Compliance with pharmacopeial purity tests is vital to protect patient health and guarantee product quality in pharmaceutical and disinfection applications.

Objectives and Study Overview

This study applies the purity test for volatile impurities in anhydrous ethanol and ethanol for disinfection as defined by the Japanese Pharmacopoeia (JP) and aligned with USP and EP standards. Key goals include verifying system suitability, quantifying methanol, acetaldehyde, acetal and benzene levels, and confirming compliance with specified volumetric limits.

Methodology

Sample and standard solutions were prepared per JP Supplement I. Ethanol for disinfection was adjusted to 83 % v/v with purified water. Impurity quantification followed equation-based limits: total acetaldehyde plus acetal ≤ 10 vol ppm and benzene ≤ 2 vol ppm.

Used Instrumentation

• Shimadzu Nexis GC-2030 gas chromatograph with AOC-20i Plus autosampler
• ZB-624 capillary column (30 m × 0.32 mm I.D., 1.8 µm film thickness)
• Flame ionization detector (FID)
• Helium carrier gas, constant linear velocity (35 cm/s)

Analysis Conditions

• Oven program: 40 °C (12 min), ramp 10 °C/min to 240 °C (10 min), total run time 42 min
• Injection: split 1:20, 1 µL, injector 200 °C, detector 280 °C

Main Results and Discussion

• System suitability: Resolution between acetaldehyde and methanol > 1.5—observed 2.01 (anhydrous) and 1.74–1.82 (disinfection).
• Methanol peak area in samples remained below half that of the standard solution.
• Total acetaldehyde + acetal levels were 0.73 vol ppm (anhydrous) and 0.36 vol ppm (disinfection), under the 10 vol ppm limit.
• Benzene was not detected, confirming levels below the 2 vol ppm threshold.
• Signal-to-noise ratios exceeded acceptance criteria, demonstrating high method sensitivity.

Benefits and Practical Applications of the Method

• Full compliance with JP, USP and EP volatile impurity requirements.
• Robust detection of benzene at sub-ppm concentrations.
• Reproducible system suitability metrics ensure reliable routine monitoring.
• Applicable as a quality control tool in pharmaceutical and disinfectant ethanol manufacturing.

Future Trends and Potential Applications

• Coupling with mass spectrometry to enhance specificity and broaden analyte scope.
• Use of faster chromatography methods to reduce analysis time and increase throughput.
• Automated sample preparation and data processing to streamline workflows.
• Extension to other solvent purity assessments and multicomponent impurity profiling.
• Implementation of greener carrier gases and solvents for sustainable analytics.

Conclusion

The Shimadzu Nexis GC-2030 GC-FID method provides reliable separation and quantification of key volatile impurities in ethanol, meeting major pharmacopeial standards. Its sensitivity and robustness support critical QA/QC operations in pharmaceutical and disinfection contexts.

Reference

• Japanese Pharmacopoeia, 17th Edition, Supplement I.
• United States Pharmacopoeia (USP) Impurities Chapter.
• European Pharmacopoeia (EP) Volatile Impurities Testing.
• Shimadzu Application Note G331, Shimadzu Corporation, First Edition: Jul. 2020.