Abstract
The Premarket Tobacco Product Applications (PMTA) guidance issued by the Food and Drug Administration for electronic nicotine delivery systems (ENDSs) recommends that in addition to reporting harmful and potentially harmful constituents (HPHCs), manufacturers should evaluate these products for other chemicals that could form during use and over time. Although e-vapor product aerosols are considerably less complex than mainstream smoke from cigarettes and heated tobacco product (HTP) aerosols, there are challenges with performing a comprehensive chemical characterization. Some of these challenges include the complexity of the e-liquid chemical compositions, the variety of flavors used, and the aerosol collection efficiency of volatile and semi-volatile compounds generated from aerosols. In this study, a non-targeted analysis method was developed using gas chromatography-mass spectrometry (GC-MS) that allows evaluation of volatile and semi-volatile compounds in e-liquids and aerosols of e-vapor products. The method employed an automated data analysis workflow using Agilent MassHunter Unknowns Analysis software for mass spectral deconvolution, peak detection, and library searching and reporting. The automated process ensured data integrity and consistency of compound identification with >99% of known compounds being identified using an in-house custom mass spectral library. The custom library was created to aid in compound identifications and includes over 1,100 unique mass spectral entries, of which 600 have been confirmed from reference standard comparisons. The method validation included accuracy, precision, repeatability, limit of detection (LOD), and selectivity. The validation also demonstrated that this semi-quantitative method provides estimated concentrations with an accuracy ranging between 0.5- and 2.0-fold as compared to the actual values. The LOD threshold of 0.7 ppm was established based on instrument sensitivity and accuracy of the compounds identified. To demonstrate the application of this method, we share results from the comprehensive chemical profile of e-liquids and aerosols collected from a marketed e-vapor product. Applying the data processing workflow developed here, 46 compounds were detected in the e-liquid formulation and 55 compounds in the aerosol sample. More than 50% of compounds reported have been confirmed with reference standards. The profiling approach described in this publication is applicable to evaluating volatile and semi-volatile compounds in e-vapor products.
Highlights
Electronic nicotine delivery system (ENDS) product usage has increased in popularity over the past decade as a potential alternative to combustible cigarettes for the adult tobacco consumer (Ayers et al, 2011; Adkison et al, 2013; Delnevo et al, 2016), and usage continues to increase (McMillen et al, 2015; Rigotti et al, 2015; Rawlinson et al, 2017)
The response for analytes in gas chromatography-mass spectrometry (GC-MS) with electron impact ionization mode (EI) varies based on compound fragmentation, which is different for all compounds
To determine the limit of detection (LOD), we evaluated the match factor score and signal-to-noise ratio (S/N) for each of the eight compounds fortified in the F1 blank e-liquid matrix samples at 0.5, 0.7, 1.0, 2.0, and 5.0 ppm
Summary
Electronic nicotine delivery system (ENDS) product usage has increased in popularity over the past decade as a potential alternative to combustible cigarettes for the adult tobacco consumer (Ayers et al, 2011; Adkison et al, 2013; Delnevo et al, 2016), and usage continues to increase (McMillen et al, 2015; Rigotti et al, 2015; Rawlinson et al, 2017). ENDSs are noncombustible tobacco products and are referred to as electronic cigarettes (e-cigs), vapes, vaporizers, vape pens, or e-vapor products Their designs have evolved from the firstgeneration devices (“cig-a-likes”) to devices with disposable, prefilled cartridges or “pods” and “mods” with usercontrollable settings, such as wattage, voltage, and temperature control (Zhu et al, 2014; Talih et al, 2017; FDA, 2019c). This guidance recommended that all ENDS products, including e-liquids and devices, be evaluated in order to ensure that these new products would be appropriate for the protection of public health These recommendations included the evaluation of both chemical and physical characterization of the product and product performance across the lifespan of the device under both intense and non-intense use conditions (FDA, 2019b). The guidance recommends reporting a specific list of harmful and potentially harmful constituents (HPHCs), as well as other constituents of toxicological concern, contained in the product or delivered by the product (FDA, 2019b). This type of analysis requires performing chemical characterization that is non-selective and provides the detection of constituents across a wide range of chemical classes, often referred to as non-targeted analysis (NTA)
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