E-cigarettes are gaining popularity in the U.S. as well as in other global markets. Currently, limited published analytical data characterizing e-cigarette formulations (e-liquids) and aerosols exist. While FDA has not published a harmful and potentially harmful constituent (HPHC) list for e-cigarettes, the HPHC list for currently regulated tobacco products may be useful to analytically characterize e-cigarette aerosols. For example, most e-cigarette formulations contain propylene glycol and glycerin, which may produce aldehydes when heated. In addition, nicotine-related chemicals have been previously reported as potential e-cigarette formulation impurities. This study determined e-liquid formulation impurities and potentially harmful chemicals in aerosols of select commercial MarkTen(®) e-cigarettes manufactured by NuMark LLC. The potential hazard of the identified formulation impurities and aerosol chemicals was also estimated. E-cigarettes were machine puffed (4-s duration, 55-mL volume, 30-s intervals) to battery exhaustion to maximize aerosol collection. Aerosols analyzed for carbonyls were collected in 20-puff increments to account for analyte instability. Tobacco specific nitrosamines were measured at levels observed in pharmaceutical grade nicotine. Nicotine-related impurities in the e-cigarette formulations were below the identification and qualification thresholds proposed in ICH Guideline Q3B(R2). Levels of potentially harmful chemicals detected in the aerosols were determined to be below published occupational exposure limits.

Low levels of thermal degradation products such as carbonyls (formaldehyde, acetaldehyde, acrolein, crotonaldehyde) have been reported in e-cigarette aerosols. The collection and analysis of e-cigarette aerosol carbonyls are often adapted from methods developed for tobacco cigarette smoke. These methodologies are often not sensitive enough to detect low carbonyl levels in e-cigarette aerosols. One objective of this work was to develop and validate a rapid, selective and sensitive ultra-performance liquid chromatography with mass spectrometry method optimized for analysis of carbonyls in e-cigarette aerosols. Aerosols were trapped in 20-puff collections, 4-s durations, 55-mL volumes, 30-s intervals, square wave puff profiles. Collection apparatus involved a linear smoking machine with Cambridge filter pad followed by a glass impinger containing acidified 2,4-dinitrophenylhydrazine. This method showed limits of quantitation and detection of 0.016 and 0.003 µg puff−1, respectively, and run time of 4 min. Six e-cigarettes were evaluated (five devices each). All contained measurable levels of carbonyls. Levels were mostly well below those in conventional cigarettes. However, for some e-cigarettes, formaldehyde levels were above those for tobacco cigarettes (highest at 14.1 µg puff−1). Temperatures related to carbonyl yields in e-cigarette aerosols were explored to better understand carbonyl formation: formation of formaldehyde is low at temperatures below 350°C.

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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