PURPOSE: The objective of this study was to develop a stability protocol for the sample preparation procedure for liquid hand sanitizer drug products. The purpose is to provide an accurate spike and recovery procedure for ethanol, isopropanol, and the level 1 impurities (methanol, benzene, acetal, and acetaldehyde). The work will enable the FDA regulators to understand the chemical changes in hand sanitizer products that may affect the accuracy of the results and impact product safety and efficacy. METHODS: The Office of Testing & Research advanced analytics team at the Division of Product Quality Research investigated the spike and recovery issues of two impurities, acetal and acetaldehyde, as well as possible stability problems that might have resulted in irregularities or inaccuracy in the analytical recovery of these two analytes in liquid hand sanitizers. Benchtop and autosampler stability studies were performed for ethanol, isopropanol, and related hand sanitizer impurities in different diluents. Kinetic stability experiments were performed for acetal, acetaldehyde, and ethanol in hand sanitizer formulations buffered at different pHs to study the chemical stability of the analytes. All analytical study samples were analyzed using a headspace GC-MS method validated according to ICH Q2(R1). RESULTS: Kinetic studies to monitor the stability of acetal, acetaldehyde, and ethanol at different pH values confirmed the instability of acetal at acidic pH. Benchtop and autosampler stability studies of ethanol, isopropanol, and level 1 impurities in dimethyl sulfoxide diluent showed stability over 72 hrs. It was determined that hand sanitizer products with acidic pH caused the spike and recovery variability of acetal and acetaldehyde, which resulted in failed spike and recovery experiments. Current studies are underway to establish the analytical mitigation procedure for acetal and acetaldehyde spike and recovery variabilities in acidic based liquid hand sanitizer product formulations. CONCLUSIONS: The chemical interconversion between acetal and acetaldehyde in acidic liquid hand sanitizer products was determined to be the cause of spike and recovery testing failure. The validated headspace GC-MS method supported CDER’s efforts to ensure the quality of hand sanitizers for public use.

Hand sanitizer analytical stability challenges and recommendations

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.