Abstract
A method for determining the fraction of free-base nicotine (α(fb)) in electronic cigarette liquids ("e-liquids") based on headspace solid-phase microextraction (h-SPME) is described. The free-base concentration c(e,fb) = α(fb)c(e,T), where c(e,T) is the total (free-base + protonated) nicotine in the liquid. For gas/liquid equilibrium of the volatile free-base form, the headspace nicotine concentration is proportional to c(e,fb) and thus also to α(fb). Headspace nicotine is proportionally absorbed with an SPME fiber. The fiber is thermally desorbed in the heated inlet of a gas chromatograph coupled to a mass spectrometer: the desorbed nicotine is measured by gas chromatography-mass spectrometry. For a second h-SPME measurement, an adequate base is added to the sample vial to convert essentially all protonated nicotine to the free-base form (α(fb) → 1.0). The ratio of the first h-SPME measurement to the second h-SPME measurement gives α(fb) in the initial sample. Using gaseous ammonia as the added base, the method was (1) verified using lab-prepared e-liquid solutions with known α(fb) values and (2) used to determine the α(fb) values for 18 commercial e-liquids. The measured α(fb) values ranged from 0.0 to 1.0. Increasing measurement error with decreasing α(fb) caused modestly lower method precision at small α(fb). Adding a liquid organic base may be more convenient than adding gaseous ammonia: one of the samples was examined using triethylamine as the added base; the measurements agreed well (with ammonia, 0.27 ± 0.01; with triethylamine, 0.26 ± 0.04). Other workers have proposed examining the nicotine protonation state in e-liquids using three steps: (1) 1:10 dilution with CO(2)-free water; (2) measurement of pH; and (3) calculation of the resulting values for α(fb,w,1:10), the free-base fraction in the diluted mostly aqueous phase. As expected and verified here, because of the generally greater abilities of organic acids to protonate nicotine in water versus in an e-liquid phase, α(fb,w,1:10) values can be significantly less than actual e-liquid α(fb) values when α(fb) is not close to either 0 or 1.