Conversion of Nicotine in Tobacco Smoke to Its Volatile and Available Free-Base Form through the Action of Gaseous Ammonia

Ammonia-forming compounds are routinely added to cigarette tobacco. The U.S. Food and Drug Administration (FDA) has argued that this is done to promote the formation of the volatile free-base form of nicotine in mainstream smoke (MSS) particles, thus increasing its availability to the smoker. The presence of ammonia in tobacco smoke may also be expected to promote the volatilization of nicotine from environmental tobacco smoke (ETS) particles in indoor air. The gas/particle partitioning of nicotine can be parameterized in terms of the gas/particle partitioning constant K p = c p/c g, where c p (ng/μg) is the concentration in the particle phase and c g (ng/m3) is the concentration in the gas phase. The ability of ammonia to increase the amount of nicotine in the gas phase, as compared to the particle phase, was measured and confirmed. A gas-phase am monia pressure of p NH3 of ∼100 × 10-6 atm (100 ppmV) was found to reduce the K p value for the partitioning of nicotine to tobacco smoke particulate matter by more than 100-fold. The agreement between ETS and MSS at p NH3 ≈ 100 ppmV was excellent, suggesting that the overall physical properties (e.g., polarity and number-average molecular weight) of ETS and MSS particulate material are very similar. Because gas-phase nicotine deposits more readily in the respiratory tract than does particle-phase nicotine and because free-base nicotine is more lipid soluble than is protonated nicotine, such a reduction in K p will increase the availability of nicotine from MSS as well as from freshly formed ETS particles. At 20 °C and a relative humidity of 60%, the partitioning constant for the free-base form of nicotine is estimated to be K p,fb = c p,fb/c g = 10-4.94. Cor rection to a body temperature of 37 °C yields K p,fb = 10-5.97. Calculations using this K p,fb value indicate that about 25% of the nicotine will be in the gas phase at a temperature of 37 °C for inhaled MSS under the full ammonia effect at a total suspended smoke particulate matter level of 3 × 106 μg/m3.