Measurement of the Free-Base Nicotine Fraction (α_fb) in Electronic Cigarette Liquids by Headspace Solid-Phase...

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_fbc_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 CO₂-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.