The nicotine used in e-cigarettes and refill e-liquids is extracted from tobacco, and its purity can vary depending upon manufacturer and grade. The US and European Pharmacopoeias make recommendations for the purity of nicotine intended for pharmaceuticals; however, there is no official purity recommendation for nicotine used in e-cigarettes. To date, there are few published reports on nicotine-related impurities in e-cigarettes and refill e-liquids. The objective of this work was to develop a sensitive, selective, and robust analytical method for the quantitation of nicotine-related impurities in e-vapor products and to evaluate the nicotine-related impurities in a variety of commercial e-cigarette cartridges (n ¼ 10) and refill e-liquids (n ¼ 10). Nicotine-N-oxide, nornicotine, mysomine, and cotinine were observed to increase with time during stability studies. This method was also applied to estimate the transfer efficiency of nicotine-related impurities to the aerosol. Most of the impurities were observed to transfer efficiently. However, nicotine-Noxides showed low transfer efficiency and demonstrated thermal degradation. This selective and sensitive method is suitable to provide quantitative data for risk assessments and for use in e-cigarette product and refill e-liquid stability studies as one of the stability-indicating measures. GRAPHICAL ABSTRACT
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