Protonation State of Nicotine in Tobacco Smoke Particulate Matter by Solid-State NMR
EMSL Project ID
3206
Abstract
Nicotine is delivered to the smoker primarily in liquid droplets that comprise tobacco smoke aerosol particulate matter (PM). Analogous with another alkaloid (cocaine), smoke-PM nicotine can exist in a free-base form (Nic) or protonated form (NicH+); this is exceedingly important for tobacco addiction. The proposed research will examine the feasibility of solid-state NMR to determine the protonation state of nicotine in commercial cigarette smoke PM.In 1994, United States cigarette makers disclosed ~600 additives to smoking tobacco (1). The intended uses of these have been subjects of much debate among the US-FDA, the public health community, and the tobacco industry. In its proposed Tobacco Rule of 1995, the FDA concluded that ammonia compounds were to enhance the free-base state of nicotine in smoke PM, thereby enhancing nicotine delivery and absorption (2). A joint response from tobacco companies (3) claimed that ammonia compounds do not have pharmacological significance in transfer of nicotine from tobacco to smoke or in nicotine absorption, and that ammonia compounds are used only for their effects on flavor and cigarette manufacture. The FDA disagreed, using tobacco industry documents and well-established concepts concerning the effects of pH on drug absorption to argue that ammonia compounds were used to affect nicotine delivery (4). We aim to address these issues directly and conclusively by NMR.
The nicotine protonation state would be most easily measured by examining the N-methyl chemical shift (1H or 13C signal) by NMR spectroscopy. We already report (5) that this works for liquid 1H-NMR when a cosolvent is present to reduce the viscosity. Liquid NMR does not work for unaltered smoke condensate, so this short, exploratory proposal is to use solid-state 13C-NMR to observe the N-methyl peak from nicotine using cigarette filters from smoked and unsmoked cigarettes. If direct CP/MAS measurement of nicotine from a smoked cigarette filter proves possible, then a larger and controlled study would be carried out, leading to CP/MAS 13C-NMR as the method of choice to provide a direct measurement of cigarette smoke nicotine acid/base chemistry.
PNNL staff would run the two spectra, and I would process and interpret. Possible collaborative publication may follow the longer-term study, if this one is successful.
(1)Tobacco Reporter, (July)1994, Staff Report
(2)US-FDA, 1995, 21 CFR Part 801, Fed. Reg. 60 (155) 41314-792
(3)Brown and Williamson Tobacco Corporation, et al., Before the US-FDA. Docket No 95N-0253 and 95N0253J, Comments, Volume III, January 2, 1996.
(4)FDA, 1996, 21 CFR Part 801, Fed. Reg. 61 (168) 44396-18
(5)Pankow, J.F., Barsanti, K.C., Peyton, D. H., 2002, Chem. Res. in Toxicol., in press
Project Details
Project type
Capability Research
Start Date
2002-12-17
End Date
2004-01-12
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
21st International Conference on the Application of Accelerators in Research and Industry (invited)
Ishimaru M, Y Zhang, and WJ Weber. 2009. "Ion-beam-induced chemical disorder in GaN." Journal of Applied Physics 106(5):053513, 1-4. doi:10.1063/1.3212555