Fraction of Free-Base Nicotine in Fresh Smoke Particulate Matter from the Eclipse "Cigarette" by 1H NMR Spectroscopy
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- 作者：James F. Pankow ; Kelley C. Barsanti ; and David H. Peyton
- 刊名：Chemical Research in Toxicology
- 出版年：2003
- 出版时间：January 2003
- 年：2003
- 卷：16
- 期：1
- 页码：23 - 27
- 全文大小：66K
- 年卷期：v.16,no.1(January 2003)
- ISSN：1520-5010
文摘
Solution 1H NMR (proton-NMR) spectroscopy was used to measure the distribution of nicotinebetween its free-base and protonated forms at 20 
C in (a) water; (b) glycerin/water mixtures;and (c) puff-averaged "smoke" particulate matter (PM) produced by the Eclipse cigarette, aso-called "harm reduction" cigarette manufactured by R. J. Reynolds (RJR) Tobacco Co. SmokePM from the Eclipse contains glycerin, water, nicotine, and numerous other components. SmokePM from the Eclipse yielded a signal for the three N-methyl protons on nicotine at a chemicalshift of 
chars/delta.gif" BORDER=0 > (ppm) = 2.79 relative to a trimethylsilane standard. With chars/alpha.gif" BORDER=0>fb = fraction of the totalliquid nicotine in free-base form, and chars/alpha.gif" BORDER=0>a = fraction in the acidic, monoprotonated NicH+ form,then chars/alpha.gif" BORDER=0>a + chars/alpha.gif" BORDER=0>fb 
1. (The diprotonated form of nicotine was assumed negligible.) When the threetypes of solutions were adjusted so that chars/alpha.gif" BORDER=0>a 1, the N-methyl protons yielded chars/delta.gif" BORDER=0 >a = 2.82 (Eclipsesmoke PM); 2.79 (35% water/65% glycerin); and 2.74 (water). When the solutions were adjustedso that chars/alpha.gif" BORDER=0>fb 1, the N-methyl protons yielded chars/delta.gif" BORDER=0 >fb = 2.16 (Eclipse smoke PM); 2.13 (35% water/65% glycerin); and 2.10 (water). In all of the solutions, the rate of proton exchange betweenNicH+ and Nic was fast relative to the 1H-NMR chemical shift difference in hertz. Each solutioncontaining both NicH+ and Nic thus yielded a single N-methyl peak at a chars/delta.gif" BORDER=0 > given by chars/delta.gif" BORDER=0 > = chars/alpha.gif" BORDER=0>achars/delta.gif" BORDER=0 >a+ chars/alpha.gif" BORDER=0>fbchars/delta.gif" BORDER=0 >fb so that chars/delta.gif" BORDER=0 > varied linearly between chars/delta.gif" BORDER=0 >a and chars/delta.gif" BORDER=0 >fb. Since chars/alpha.gif" BORDER=0>fb = (chars/delta.gif" BORDER=0 >a - chars/delta.gif" BORDER=0 >)/(chars/delta.gif" BORDER=0 >a - chars/delta.gif" BORDER=0 >fb), then chars/delta.gif" BORDER=0 > =2.79 for the unadjusted Eclipse smoke PM indicates chars/alpha.gif" BORDER=0>fb 0.04. The effective pH of the Eclipsesmoke PM at 20 C may then be calculated as pHeff = 8.06 + log[chars/alpha.gif" BORDER=0>fb/(1 - chars/alpha.gif" BORDER=0>fb)] = 6.69, where8.06 is the pKa of NicH+ in water at 20 C. The measurements obtained for the puff-averagedEclipse smoke PM pertain to the chemistry of the smoke PM as it might be initially inhaledat 20 C. Upon inhalation, the volatilization of nicotine and other acid/base active compounds(as well as a warming toward a body temperature of 37 C) will alter the pHeff value of thesmoke PM during the time that it resides and ages in the respiratory tract.
C in (a) water; (b) glycerin/water mixtures;and (c) puff-averaged "smoke" particulate matter (PM) produced by the Eclipse cigarette, aso-called "harm reduction" cigarette manufactured by R. J. Reynolds (RJR) Tobacco Co. SmokePM from the Eclipse contains glycerin, water, nicotine, and numerous other components. SmokePM from the Eclipse yielded a signal for the three N-methyl protons on nicotine at a chemicalshift of chars/delta.gif" BORDER=0 > (ppm) = 2.79 relative to a trimethylsilane standard. With chars/alpha.gif" BORDER=0>fb = fraction of the totalliquid nicotine in free-base form, and chars/alpha.gif" BORDER=0>a = fraction in the acidic, monoprotonated NicH+ form,then chars/alpha.gif" BORDER=0>a + chars/alpha.gif" BORDER=0>fb 1. (The diprotonated form of nicotine was assumed negligible.) When the threetypes of solutions were adjusted so that chars/alpha.gif" BORDER=0>a 1, the N-methyl protons yielded chars/delta.gif" BORDER=0 >a = 2.82 (Eclipsesmoke PM); 2.79 (35% water/65% glycerin); and 2.74 (water). When the solutions were adjustedso that chars/alpha.gif" BORDER=0>fb 1, the N-methyl protons yielded chars/delta.gif" BORDER=0 >fb = 2.16 (Eclipse smoke PM); 2.13 (35% water/65% glycerin); and 2.10 (water). In all of the solutions, the rate of proton exchange betweenNicH+ and Nic was fast relative to the 1H-NMR chemical shift difference in hertz. Each solutioncontaining both NicH+ and Nic thus yielded a single N-methyl peak at a chars/delta.gif" BORDER=0 > given by chars/delta.gif" BORDER=0 > = chars/alpha.gif" BORDER=0>achars/delta.gif" BORDER=0 >a+ chars/alpha.gif" BORDER=0>fbchars/delta.gif" BORDER=0 >fb so that chars/delta.gif" BORDER=0 > varied linearly between chars/delta.gif" BORDER=0 >a and chars/delta.gif" BORDER=0 >fb. Since chars/alpha.gif" BORDER=0>fb = (chars/delta.gif" BORDER=0 >a - chars/delta.gif" BORDER=0 >)/(chars/delta.gif" BORDER=0 >a - chars/delta.gif" BORDER=0 >fb), then chars/delta.gif" BORDER=0 > =2.79 for the unadjusted Eclipse smoke PM indicates chars/alpha.gif" BORDER=0>fb 0.04. The effective pH of the Eclipsesmoke PM at 20 C may then be calculated as pHeff = 8.06 + log[chars/alpha.gif" BORDER=0>fb/(1 - chars/alpha.gif" BORDER=0>fb)] = 6.69, where8.06 is the pKa of NicH+ in water at 20 C. The measurements obtained for the puff-averagedEclipse smoke PM pertain to the chemistry of the smoke PM as it might be initially inhaledat 20 C. Upon inhalation, the volatilization of nicotine and other acid/base active compounds(as well as a warming toward a body temperature of 37 C) will alter the pHeff value of thesmoke PM during the time that it resides and ages in the respiratory tract.