A novel protocol for quantitative determination of 1,4-dioxane in finished cleaning products
by Brian Palumbo, Deena Conrad-Vlasak, Kathleen Stanton
A novel method to quantify 1,4-dioxane in finished cleaning products using headspace gas chromatograph with mass spectrometry (HS GC/MS), single ion monitoring, and a fully deuterated internal standard has been developed. The method generates very linear calibration curves with a R2 of at least 0.99, excellent accuracy with spike/recovery of 97%–102%, and effective precision of 1%–7%RSD for different cleaning products. The method also produces an instrument limit of quantitation (LOQ) of <20 ppb, and sample LOQ of <100 ppb. The method robustness was demonstrated with a ten-lab round-robin exercise that showed that even with some unexpected deviations from the method, excellent analytical results were obtained from the different labs. This new method will be valuable to evaluate consumer products impacted by government regulation to limit 1,4-dioxane concentrations in complex matrices.
1,4-Dioxane is a chemical impurity that can commonly be found in a variety of commercial products, especially those that use ethoxylated surfactants (Agency for Toxic Substances and Disease Registry (ATSDR), 2012). It is a substance of concern after being classified as a potential human carcinogen by multiple regulatory authorities and other organizations (U.S. Department of Health and Human Services (DHHS), 2016; EPA, 2013; European Chemicals Bureau (ECB), 2002; National Institute for Occupational Safety and Health (NIOSH), 2010). Product manufacturers are reducing the levels of 1,4-dioxane in household products by optimizing the production processes of ethoxylated surfactants, favoring base-catalyzed processes over acid catalysis, using vacuum stripping to remove volatile impurities, and derivatizing the surfactants.
The concerns of 1,4-dioxane are leading to increased scrutiny and regulation by a variety of government bodies. New York’s legislature has passed limits on 1,4-dioxane in household cleaning, personal care, and cosmetic products starting in December 2022 which will be regulated under the Department of Environmental Conservation (DEC). These limits will range from 1 to 10 ppm (New York State Department of Environmental Conservation, n.d.). The California Department of Toxic Substances and Control (DTSC) is also considering consumer product regulations on 1,4-dioxane (California Department of Toxic Substances Control, n.d.).
To understand the amount of 1,4-dioxane in consumer products, sensitive analytical methods are required. There are many different analytical methods in the literature for 1,4-dioxane that can be used at different levels of analyte, different matrices, and using different kinds of instrumentation (Hayes et al., 2022). Most of these methods are focused on analyzing drinking water, a much simpler matrix than consumer cleaning products. Existing methods point to the benefits of different parts of the analysis, including gas chromatography (GC) (Cortellucci & Dietz, 1999), headspace (HS) sampling (Shin & Lim, 2011), mass spectrometry (MS) (Fuh et al., 2005), and using internal standards (IS) (Draper et al., 2000; Sun et al., 2016). However, the analysis of consumer products is complicated by the other components of these complex formulations. Previous methods have been developed to address these concerns using GC/MS, but many have employed either more complex sample preparation schemes or more complex MS techniques (Tanabe & Kawata, 2019; Zhou, 2019). The best and most useful of the previous work for these purposes was using static HS, GC/MS, and an isotopic IS by Tahara et al. (Tahara et al., 2013) These different published methods provide guidance when developing a new method to ensure sufficient sensitivity for sub-ppm quantitation, effectiveness across different cleaning product categories, relatively simple approaches using simpler testing techniques, and robustness across many different labs. The key learnings include the use of a chemically similar internal standard which negates any matrix effects, simple analyte extraction from complex formulations, use of chromatographic separation to isolate the analyte of interest, and highly sensitive detection that is specific to the analyte.
The method described below fulfills all these important criteria and addresses the needs as described in Hayes et al. (2022) We have developed the method with a deuterated internal standard which is chemically identical to the analyte under these conditions. We use headspace analyte extraction to optimize the delivery of 1,4-dioxane because it is applicable over the wide range of sample matrices present in the complex formulations of consumer products. Once in the instrument, we favor gas chromatography coupled with mass spectrometry with selective ion monitoring to provide specific and sensitive detection and quantitation of the 1,4-dioxane.
Once developed, we sought to validate the methodology through a ten-lab round robin exercise using contract, industrial and academic analytical laboratories. Representative cleaning product formulations were produced to simulate laundry and hand dish detergents used in both consumer and industrial, institutional, and commercial settings as these are some of the product categories regulated under NYS DEC and are categories under consideration for regulations by CA DTSC.
MATERIALS AND METHODS
A certified reference standard of 99.8% pure 1,4-dioxane was purchased from Sigma Aldrich (CRM48367). A 99% pure, fully deuterated 1,4-dioxane-d8 standard was purchased from Sigma-Aldrich (catalog number 186406) or Alfa Aesar (catalog number 36516). This is used as the IS.
Finished cleaning materials were modeled from common off-the-shelf consumer products. Each has a specified amount of surfactant in a water base. The relative concentrations of the components are included in Appendix A (Tables A1 and A2):
- Hand dish soap 1 (30% surfactant in water)
- Hand dish soap 2 (15% surfactant in water)
- Consumer laundry detergent 1 (15% surfactant in water)
- Consumer laundry detergent 2 (50% surfactant in water)
- Industrial and institutional (I&I) laundry detergent (50% surfactant in water)
This protocol uses HS GC coupled to MS (GC/MS) to quantify 1,4-dioxane in finished cleaning products. The protocol has been shown to be robust in terms of specific instrument and the fine details of the experimental method. The original method featured an Agilent 7679A HS unit coupled with an Agilent 6890 GC with a Zebron, ZB-624, 60 m × 0.25 mm × 1.4 μm column and 1.1 mL/min helium carrier gas flow. Samples were analyzed with a split ratio of 3:1 in an Agilent 5973 single quadrupole MSD with electron ionization (EI) using selective ion monitoring. Both total ion chromatograms (TIC) and specific extracted ion chromatograms (EIC) are shown. The full instrumental experimental conditions from the protocol are included as Appendix B.
Calibration standards of 1,4-Dioxane in DI water were prepared at concentrations ranging from 50 ppb to 2 ppm, and used in the same day as the preparation. Dimethyl sulfoxide (DMSO) has also been determined to be a suitable solvent for standard and sample preparation. A 1 mL aliquot of each standard solution was transferred to a 10 mL headspace vial, to which, 0.1 mL of a 5 ppm 1,4-dioxane-d8 internal standard solution was added prior to analysis.
Six preparations of each sample were made to determine the method precision. Accuracy and recovery were determined by making three preparations of each sample that were spiked with 0.02 ppm of 1,4-dioxane, driven by the LOQ of the method. After sample solutions were prepared, a 1 mL aliquot of each solution was transferred to a 10 mL headspace vial, to which, 0.1 mL of a 5 ppm 1,4-dioxane-d8 internal standard solution was added prior to analysis.
Under these experimental conditions, the 1,4-dioxane and 1,4-dioxane-d8 internal standard will coelute at retention time of 9.6 min. EIC were utilized to differentiate between the 1,4-dioxane and 1,4-dioxane-d8 present in sample and standard chromatograms. 1,4-Dioxane was quantified by integrating the peak area of the 88 u EIC peak, using 58 u as a qualifying peak. 1,4-Dioxane-d8 was quantified by integrating the peak area of the 96 u EIC peak. Figure 1 shows the results for a 1 ppm 1,4-dioxane standard with the TIC at the top, the 88 u EIC for the standard in the middle, and the 96 u EIC for the internal standard at the bottom. The standard and internal standard are easily identified and quantified using this method with no meaningful interferences from the water or introduced by the method. Calibration standards were analyzed in the middle and at the end of the analysis sequence.
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