Through Container Quantitative Screening of Hand Sanitizers

Published in Chemistry
Through Container Quantitative Screening of Hand Sanitizers

Share this post

Choose a social network to share with, or copy the shortened URL to share elsewhere

This is a representation of how your post may appear on social media. The actual post will vary between social networks

Hand Hygiene and COVID-19

Hand hygiene is an important part of the response to the Coronavirus Disease 2019 (COVID-19) pandemic.1 Washing hands with soap and water for 20 seconds is highly recommended, especially before eating and after coughing, sneezing, blowing nose or going to the bathroom. If soap and water are not readily available, use of alcohol (ethanol or isopropanol) based hand sanitizers are recommended by the WHO2 and the CDC3 at concentrations 60-80 % v/v. Due to the public health emergency posed by COVID-19, consumers and health care providers were having difficulty accessing alcohol-based hand sanitizer products.  As a result, domestic production of hand sanitizers has increased, and other hand sanitizer products were imported into the US market.  Since then, numerous hand sanitizer products (domestic or imported) were found to be out of specification and/or contaminated with methanol or 1-propanol.4 Methanol contaminated hand sanitizer products (when used as directed) can cause chronic toxicity and the ingestion of these contaminated products can be fatal.5 Moreover, because alcohol-based hand sanitizers are recommended for use at certain concentrations of the active ingredient (ethanol or isopropanol), products that are out of specification by being sub-potent also pose risks to consumers. A high-quality alcohol-based hand sanitizer supply can be monitored by frequent testing. Unfortunately, standard gas chromatography (GC)-based hand sanitizer testing for impurities or assay require a tedious and time-consuming procedure that can be sensitive to interference from non-active ingredients in these products. Thus, a rapid screening method is desired that can identify highly contaminated, low-quality products so they can be prioritized for detailed laboratory-based analysis and assist in their expeditious removal from the supply chain.

Rapid Screening Hand Sanitizer Products

Rapid screening tools such as portable X-ray fluorometers, infrared and Raman spectrometers are employed at ports, borders, and security checkpoints. In rapid screening, much of the focus recently has been on through-container spectroscopy because such measurements require no sample preparation and allow analysis without opening and potentially spoiling products. Spatially offset Raman spectroscopy (SORS) is a technique that allows acquisition of a molecular fingerprint spectrum of a product through a container. Portable SORS devices can penetrate most plastic and glass containers (except those that are designed to block infrared and visible light).

Generally, identification is made by comparing the sample spectrum against a commercial or local library of spectra from chemicals, compounds and reagents. The comparison is made by calculating the correlation of the test sample spectrum with library spectra and ranking best matching candidates using a computer algorithm. Alcohol-based hand sanitizers are mostly made of alcohol and water, although small amounts of hydrogen peroxide, glycerin, aloe, polymers, and oils can be present depending on the formulation. Due to effects related to hydrogen bonding in alcohol-water mixtures, Raman and IR peak positions of alcohols can manifest large shifts. Matrix effects in finished products such as alcohol-water mixture effects in hand sanitizers present challenges to raw or pure chemical library based identification in rapid screening. 

Quantitative Through-Container Analysis

Commercially available products such as a hand sanitizer can be found in various sizes, shapes, and types of containers. Because different containers allow transmission of light in different amounts, the exact intensity of light interacting with the contents in through-container analysis will not be known. However, the matrix effects in finished products such as spectral shifts in alcohol-water mixtures can be utilized with advanced chemometrics to allow quantitative analysis independently of the amount of light transmission.

In this study, the amount of alcohol in hand sanitizer formulations were quantified using SORS and support vector machine (SVM) based regression algorithms in containers with different material, thickness, or opacity. Quantitative measurements were achieved by taking advantage of the concentration dependence of the spectral shifts in alcohol-water mixtures as well as relative intensities of contents. Focusing on the common adulterants methanol and 1-propanol, in addition to the acceptable ingredients ethanol and isopropanol, commercial (gel or liquid) and in-house made hand sanitizer samples were quantified with high accuracy (2-5% root-mean-square error) in many different types of plastic and glass containers with varying degrees of opacity. Out of 53 commercial samples, only two of them did not yield a high-quality spectrum using SORS. In total 173 samples were tested, 60 of the 65 (92% e.g., passing) in specification, 20 of the 24 out-of-specification (83%, e.g., sub-potent), and 77 of the 84 contaminated samples (e.g., containing methanol or 1-propanol, 92%) were accurately identified.

Using the method developed in this study, non-invasive, through-container quantitative analysis can be completed within seconds and help sort samples for confirmatory testing by GC or other techniques. Screening medical countermeasures and other products rapidly and non-invasively can be critical to overcoming challenges in drug shortages and quality of drug products during public health emergencies.


  1. FDA Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19) Guidance for Industry (Accessed August 2020).
  2. World Health, O.; Safety, W. H. O. P., WHO guidelines on hand hygiene in health care. World Health Organization: Geneva, 2009.
  3. CDC Hand Hygiene Recommendations.
  4. FDA Updates on hand sanitizers consumers should not use (Accessed August 2021).
  5. Overbeek, D. L.; Watson, C. J.;  Castaneda, N. R.; Ganetsky, M., A Geographically Distinct Case of Fatal Methanol Toxicity from Ingestion of a Contaminated Hand Sanitizer Product During the COVID-19 Pandemic. J Med Toxicol 2021, 17 (2), 218-221.

Please sign in or register for FREE

If you are a registered user on Research Communities by Springer Nature, please sign in

Subscribe to the Topic

Physical Sciences > Chemistry

Related Collections

With collections, you can get published faster and increase your visibility.

Coacervation in systems chemistry

This Guest Edited Collection aims to bring together research at the intersection of systems chemistry and coacervation. We welcome both experimental and theoretical studies.

Publishing Model: Open Access

Deadline: Dec 31, 2023

Plasmon-mediated chemistry

This collection aims to cover a comprehensive range of topics related to plasmon-mediated chemical reactions.

Publishing Model: Open Access

Deadline: Jan 31, 2024