A determination of the aerosolization efficiency of drugs of abuse in a eutectic mixture with nicotine in electronic cigarettes

Abstract

Characterize the effects of drug interactions with nicotine in the electronic cigarette (e-cigarette). E-liquids are composed of vegetable glycerin (VG), propylene glycol (PG), an active ingredient such as nicotine, and flavorings (Mulder, H.A., et al., Sci Rep., 2019, 9, 102201). Users can adulterate e-liquids with other pharmacologically active substances (Varlet, V. Toxics, 2016, 4, 29). The interaction between the diluent and nicotine forms a eutectic mixture, reducing the melting point to a temperature lower than the individual compounds and promoting aerosolization of the drugs (Gala, U., et al. J Dev Drugs., 2013, 2, e130). The purpose of this study was to evaluate the effect of nicotine on the aerosolization efficiency and recovery of methadone and cocaine using an aerosol capture method adopted from the established Cooperation Centre for the Scientific Research Relative to Tobacco (CORESTA) E-cigarette Task Force industry method. Individual e-liquids were prepared with 12 mg/mL nicotine, methadone, and cocaine in 1:1 PG:VG and drug-free. Aerosol capture was performed using parameters adopted from the CORESTA method. The puff profile was an inhale duration of 3 seconds, an exhale duration of 10 seconds, and a puff volume of 60 mL for a total of 15 puffs. A method for quantitation was validated on a Gas Chromatograph-Mass Spectrometer over five days. The linear range for nicotine was determined to be 500–20,000 ng/mL. Bias and precision were evaluated using quality controls prepared at 1500, 8000, and 16,000 ng/mL. The linear range for methadone and cocaine was 50–5000 ng/mL. Bias and precision were evaluated using quality controls prepared at 150, 1500, and 4000 ng/mL. Carryover was determined for all compounds by evaluating a blank after the injection of the highest calibrator. Aerosol samples were analyzed for drug recovery and dose. Samples were also evaluated for the pyrolytic products of nicotine, methadone, and cocaine: β-nicotyrine (nicotine), EDDP (methadone), and benzoic acid and anhydroecgonine methyl ester (cocaine). The average linear regression ( n = 5) for nicotine, methadone, and cocaine had an r2 > 0.996. Bias and precision for all analytes were within ± 9% and ± 12%CV, respectively. No carryover was observed. In the single drug e-liquids prepared at 12 mg/mL ( n = 3), 1.6 ± 0.2 mg of nicotine, 2.7 ± 0.1 mg of methadone, and 0.94 ± 0.04 mg of cocaine were aerosolized. In the nicotine/methadone mixture ( n = 3), nicotine and methadone increased to 3.7 ± 0.5 mg and 3.7 ± 0.1 mg, respectively. In the nicotine/cocaine mixture ( n = 3), nicotine and cocaine increased to 5.7 ± 2 mg and 2.7 ± 0.2 mg, respectively. In the 15 puffs of the nicotine, methadone, and cocaine e-liquids, 0.22 ± 0.02 g, 0.31 ± 0.01 g, and 0.15 ± 0.02 g ( n = 3) were aerosolized, respectively. In the nicotine/methadone mixture, 0.37 ± 0.01 g ( n = 3) of e-liquid was aerosolized. In the nicotine/cocaine mixture, 0.38 ± 0.02 g ( n = 3) was aerosolized. Pyrolytic products were identified in the e-liquids and aerosol samples, and therefore were not a result of aerosolization. E-liquids containing nicotine and other drugs create a eutectic mixture and can increase the amount of drug delivered in the aerosol. Increases in dose from combining drugs in an e-liquid may result in adverse reactions. The formation of pyrolytic products did not impact the aerosolization efficiency of the parent drugs; however, their presence may cause unexpected effects. The eutectic mixture can result in an increase in aerosolized drug doses.