The research progress on determination of free-base nicotine in tobacco and tobacco products in the past 30 years was reviewed and discussed, including solvent extraction method, headspace solid-phase microextraction method,1H NMR, Henderson-Hasselbalch method and spectroscopy method, etc. Advantages and limitations of each method were summarized and discussed and the development in this field was prospected.

Publication Date


First Page


Last Page





[1] 王瑞新.烟草化学[M].北京:中国农业出版社,2003:67-68.WANG Rui-xin.Nicotine chemistry[M].Beijing:China Agriculture Press,2003:67-68.
[2] 史宏志,张建勋.烟草生物碱[M].北京:中国农业出版社,2004:7-27.SHI Hong-zhi,ZHANG Jian-xun.Tobacco alkaloid[M].Beijing:China Agriculture Press,2004:7-27.
[3] 王裔耿,秦云华,陆舍铭,等.主流烟气总粒相物中游离烟碱测定方法综述[J].云南化工,2007(4):59-62.WANG Yi-geng,QIN Yun-hua,LU She-ming,et al.Review of determination methods of free-base nicotine in total particulate matter of mainstream smoke[J].Yunnan Chemical Technology,2007(4):59-62.
[4] 烟草种植编写组编写.烟草化学与分析[M].北京:中国财政经济出版社,1992:17-19.Prepared by the Tobacco Cultivation Writing Group.Tobacco chemistry and analysis[M].Beijing:China Financial and Economic Publishing House,1992:17-19.
[5] 韩富根.烟草化学[M].北京:中国农业出版社,2010:88-89.HAN Fu-gen.Nicotine chemistry[M].Beijing:China Agriculture Press,2010:88-89.
[6] POURCHEZ J,PARISSE S,SARRY G,et al.Impact of power level and refill liquid composition on the aerosol output and particle size distribution generated by a new-generation e-cigarette device[J].Aerosol Science and Technology,2018,52(4):359-369.
[7] OLDHAM M J,ZHANG J,RUSYNIAK M J,et al.Particle size distribution of selected electronic nicotine delivery system products[J].Food and Chemical Toxicology,2018,113:236-240.
[8] SON Y,MAINELIS G,DELNEVO C,et al.Investigating e-cigarette particle emissions and human airway depositions under various e-cigarette-use conditions[J].Chemical Research in Toxicology,2020,33(2):343-352.
[9] PANKOW J F.A consideration of the role of gas/particle partitioning in the deposition of nicotine and other tobacco smoke compounds in the respiratory tract[J].Chemical Research in Toxicology,2001,14(11):1 465-1 481.
[10] FERRIS WAYNE G.Brand differences of free-base nicotine delivery in cigarette smoke:The view of the tobacco industry documents[J].Tobacco Control,2006,15(3):189-198.
[11] WYRZYKOWSKI D,HEBANOWSKA E,NOWAK-WICZK G,et al.Thermal behaviour of citric acid and isomeric aconitic acids[J].Journal of Thermal Analysis and Calorimetry,2011,104(2):731-735.
[12] TAKANO M,NAGAHIRO M,YUMOTO R.Transport mechanism of nicotine in primary cultured alveolar epithelial cells[J].Journal of Pharmaceutical Sciences,2016,105(2):982-988.
[13] TAKANO M,KAMEI H,NAGAHIRO M,et al.Nicotine transport in lung and non-lung epithelial cells[J].Life Sciences,2017,188:76-82.
[14] BOWEN A X C.Nicotine salt formulations for aerosol devices and methods thereof:US 09215895[P].2015-12-22.
[15] O’CONNELL G,PRITCHARD J D,PRUE C,et al.A randomised,open-label,cross-over clinical study to evaluate the pharmacokinetic profiles of cigarettes and e-cigarettes with nicotine salt formulations in US adult smokers[J].Intern Emerg Med,2019,14(6):853-861.
[16] HWA Jung B,CHUL Chung B,CHUNG S J,et al.Different pharmacokinetics of nicotine following intravenous administration of nicotine base and nicotine hydrogen tartarate in rats[J].Journal of Controlled Release,2001,77(3):183-190.
[17] HENNINGFIELD J,PANKOW J,GARRETT B.Ammonia and other chemical base tobacco additives and cigarette nicotine delivery:Issues and research needs[J].Nicotine & Tobacco Research,2004,6(2):199-205.
[18] HARVANKO A M,HAVEL C M,JACOB P,et al.Characterization of nicotine salts in 23 electronic cigarette refill liquids[J].Nicotine Tob Res,2020,22(7):1 239-1 243.
[19] 卢斌斌,谢剑平,刘惠民.烟草中游离烟碱与其pH值之间的关系[J].烟草科技,2003(6):6-10.LU Bin-bin,XIE Jian-ping,LIU Hui-min.Relationship between free nicotine in tobacco and its pH value[J].Tobacco Science & Technology,2003(6):6-10.
[20] 杜珊,吴寅初,姚忠达.烟草中游离烟碱水萃取体系定量分析方法[J].安徽大学学报(自然科学版),2006(5):91-94.DU Shan,WU Yin-chu,YAO Zhong-da.Study on quantitative analysis method of free nicotine in tobacco by aqueous extraction system[J].Journal of Anhui University(Natural Sciences),2006(5):91-94.
[21] 殷全玉,杨铁钊,郭宝银,等.紫外分光光度法测定烟草中的游离烟碱[J].中国烟草科学,2008,29(6):20-22.YIN Quan-yu,YANG Tie-zhao,GUO Bao-yin,et al.Determinationof free-base nicotine in tobacco by ultraviolet spectrophotometry[J].Chinese Tobacco Science,2008,29(6):20-22.
[22] 李维莉,马银海,段姚俊,等.紫外分光光度法测定烟草中的游离烟碱[J].安徽农业科学,2012,40(6):3 600-3 601.LI Wei-li,MA Yin-hai,DUAN Yao-jun.Determination of free-base nicotine in tobacco by ultraviolet spectrophotometry[J].Journal of Anhui Agricultural Sciences,2012,40(6):3 600-3 601.
[23] EL-HELLANI A,EL-HAGE R,BAALBAKI R,et al.Free-base and protonated nicotine in electronic cigarette liquids and aerosols[J].Chem Res Toxicol,2015,28(8):1 532-1 537.
[24] 李剑政,郭文,万吉纯.超高效合相色谱测定电子烟油和气溶胶中游离态和质子化尼古丁含量[J].科技与创新,2020(4):139-140.LI Jian-zheng,GUO Wen,WAN Ji-chun.Determination of free-base and protonated nicotine in e-liquids and aerosols by Ultra-high performance combined phase chromatography[J].Science and Technology & Innovation,2020(4):139-140.
[25] GHOLAP V V,HEYDER R S,KOSMIDER L,et al.An Analytical perspective on determination of free base nicotine in e-liquids[J].J Anal Methods Chem,2020,2 020:6178570.
[26] 卢乐华,茹洁雄,李祥林,等.电子烟液中游离态和质子态烟碱的测定及分布[J].烟草科技,2021,54(8):36-44.LU Le-hua,RU Jie-xiong,LI Xiang-lin,et al.Determination and distribution of free-base and protonated nicotine in e-liquids[J].Tobacco Science & Technology,2021,54(8):36-44.
[27] 张槐苓,葛翠英,穆怀静.烟草分析与检验[M].郑州:河南科学技术出版社,1994:271-272.ZHANG Huai-ling,GE Cui-ying,MU Huai-jing.Tobacco analysis and testing[M].Zhengzhou:Henan Science and Technology Press,1994:271-272.
[28] 卢斌斌,谢剑平,刘惠民.卷烟烟气pH与烟气总粒相物中游离烟碱的关系[J].中国烟草学报,2005(6):7-16.LU Bin-bin,XIE Jian-ping,LIU Hui-min.Relationship between free-base nicotine in total particulate matter and pH of cigarette smoke[J].Acta Tabacaria Sinica,2005(6):7-16.
[29] 张红,朱瑞芝,孟昭宇,等.卷烟主流烟气中游离烟碱的测定及分布分析[J].理化检验:化学分册,2014,50(11):1 444-1 447.ZHANG Hong,ZHU Rui-zhi,MENG Zhao-yu,et al.Determination and distribution of free-base nicotine in cigarette mainstream smoke[J].Physical Testing and Chemical Analysis Part B:Chemical Analysis,2014,50(11):1 444-1 447.
[30] GHOLAP V V,KOSMIDER L,GOLSHAHI L,et al.Nicotine forms:Why and how do they matter in nicotine delivery from electronic cigarettes?[J].Expert Opin Drug Deliv,2020,17(12):1 727-1 736.
[31] 傅若农.固相微萃取(SPME)近几年的发展[J].分析试验室,2015,34(5):602-620.FU Ruo-nong.The development of solid phase microextraction(SPME)in recent years[J].Chinese Journal of Analysis Laboratory,2015,34(5):602-620.
[32] 张凤梅,蒋薇,刘春波,等.HS-SPME-GC-MS/MS法测定不同吸烟者唾液中的7种生物碱[J].烟草科技,2018,51(7):46-53.ZHANG Feng-mei,JIANG Wei,LIU Chun-bo,et al.Headspace solid-phase microextraction coupled with gas chromatography tandem mass spectrometry for determining 7 alkaloids in saliva from smokers[J].Tobacco Science & Technology,2018,51(7):46-53.
[33] YANG S S,SMETENA I J C.Determination of tobacco alkaloids using solid phase microextraction and GC-NPD[J].Chromatographia,1998,47(7):443-448.
[34] PANKOW J F,TAVAKOLI A D,LUO W,et al.Percent free base nicotine in the tobacco smoke particulate matter of selected commercial and reference cigarettes[J].Chemical Research in Toxicology,2003,16(8):1 014-1 018.
[35] WATSON C H,TROMMEL J S,ASHLEY D L.Solid-Phase Microextraction-based approach to determine free-base nicotine in trapped mainstream cigarette smoke total particulate matter[J].Journal of Agricultural and Food Chemistry,2004,52(24):7 240-7 245.
[36] BAO M,JOZA P,RICKERT W S,et al.An improved headspace solid-phase microextraction method for the analysis of free-base nicotine in particulate phase of mainstream cigarette smoke[J].Anal Chim Acta,2010,663(1):49-54.
[37] TANG L,YANG H W,HE L,et al.Direct analysis of free-base nicotine in tobacco leaf by headspace solid-phase micro-extraction combined with gas chromatography/mass spectrometry[J].Accredit Qual Assur,2019,24(5):341-349.
[38] LAUTERBACH J H,BAO M,JOZA P J,et al.Free-base nicotine in tobacco products Part I:Determination of free-base nicotine in the particulate phase of mainstream cigarette smoke and the relevance of these findings to product design parameters[J].Regulatory Toxicology and Pharmacology,2010,58(1):45-63.
[39] BARSANTI K C,LUO W,ISABELLE L M,et al.Tobacco smoke particulate matter chemistry by NMR[J].Magn Reson Chem,2007,45(2):167-170.
[40] DUELL A K,PANKOW J F,PEYTON D H.Free-base nicotine determination in electronic cigarette liquids by1H NMR spectroscopy[J].Chem Res Toxicol,2018,31(6):431-434.
[41] PANKOW J F,BARSANTI K C,PEYTON D H.Fraction of free-base nicotine in fresh smoke particulate matter from the eclipse "cigarette" by1H NMR spectroscopy[J].Chemical Research in Toxicology,2003,16(1):23-27.
[42] MEEHAN-ATRASH J,DUELL A K,MCWHIRTER K J,et al.Free-base nicotine is nearly absent in aerosol from IQOS heat-not-burn devices,as determined by1H NMR spectroscopy[J].Chem Res Toxicol,2019,32(6):974-976.
[43] MORIE G P.Fraction of protonated and unprotonated nicotine in tobacco smoke at various pH values[J].Tob Sci,1972,16:167.
[44] RICHTER P,SPIERTO F W.Surveillance of smokeless tobacco nicotine,pH,moisture,and unprotonated nicotine content[J].Nicotine Tob Res,2003,5(6):885-889.
[45] Notice regarding requirement for annual submission of the quantity of nicotine contained in smokeless tobacco products manufactured,imported,or packaged in the United States.Centers for Disease Control and Prevention(CDC),Department of Health and Human Services.Notice[J].Federal register,1999,64(55):14 085-14 096.
[46] LAUTERBACH J H,BAO M,JOZA P J,et al.Free-base nicotine in tobacco products Part II:Determination of free-base nicotine in the aqueous extracts of smokeless tobacco products and the relevance of these findings to product design parameters[J].Regul Toxicol Pharmacol,2011,59(1):8-18.
[47] LAWLER T S,STANFILL S B,ZHANG L,et al.Chemical characterization of domestic oral tobacco products:Total nicotine,pH,unprotonated nicotine and tobacco-specific N-nitrosamines[J].Food and Chemical Toxicology,2013,57:380-386.
[48] 李国政,邱建华,周浩,等.卷烟烟气pH值研究进展[J].食品与机械,2017,33(5):216-219.LI Guo-zheng,QIU Jian-hua,ZHOU Hao,et al.Advantage of pH value in cigarette smoke[J].Food & Machinery,2017,33(5):216-219.
[49] 徐茂田,祁瑞芳,高秋梅.溴甲酚绿光度法测定烟草中的烟碱[J].理化检验:化学分册,1998,34(2):78-81.XU Mao-tian,QI Rui-fang,GAO Qiu-mei.Photometric determination of nicotine in tobacco by bromocresol green[J].Physical Testing and Chemical Analysis Part B:Chemical Analysis,1998,34(2):78-81.
[50] HUANG Y J,DENG Q X,LAN H Q,et al.Colorimetric assay for the rapid determination of free-base nicotine in e-liquid[J].Analytical Methods,2020,12(2):193-199.
[51] 黄延俊,方钲中,张廷贵,等.光谱法测定电子烟液中的游离烟碱[J].烟草科技,2021,54(8):45-51,86.HUANG Yan-jun,FANG Zheng-zhong,ZHANG Ting-gui,et al.Spectroscopic determination of free-base nicotine in e-liquids[J].Tobacco Science & Technology,2021,54(8):45-51,86.
[52] 卢丽娟,张弘韬,周浩,等.烟草中游离态烟碱的测定[J].安徽农业科学,2009,37(36):7 946-7 947,7 956.LU Li-juan,ZHANG Hong-tao,ZHOU Hao,et al.Determination on free nicotine in tobacco[J].Journal of Anhui Agricultural Sciences,2009,37(36):7 946-7 947,7 956.
[53] 艾明欢,郑赛晶,王申,等.含水率和pH对口含烟中游离烟碱含量的影响[C]//上海市烟草学会.上海市烟草专卖局2015年度获奖论文专刊.上海:上海市烟草学会,2016:5.AI Ming-huan,ZHENG Sai-jing,WANG Shen,et al.Effect of water and pH on the content of free nicotine in oral tobacco[C]//Shanghai Tobacco Society.Special Issue on 2015 Award Winning Papers of Shanghai Tobacco Monopoly Bureau.Shanghai:Shanghai Tobacco Society,2016:5.
[54] WEI Jian-ke,LAI Dong-hui,MAO Han-bing,et al.Study on determination of free-base nicotine in flue-cured tobacco with water extraction[J].Guangzhou Chemical Industry,2016,44(23):92-94.
[55] 廖头根,者为,何靓,等.顶空固相微萃取法直接测定烟叶中的游离烟碱[C]//云南省烟草学会工业专业委员会2011年学术年会论文集.昆明:云南省烟草学会工业专业委员会,2011:37-50.LIAO Tou-gen,ZHE Wei,HE Liang,et al.Direct determination of free nicotine in tobacco leaves by headspace solid phase microextraction[C]//Proceedings of 2011 Academic Annual Meeting of Industrial Committee of Yunnan Tobacco Association.Kunming:Industrial Committee of Yunnan Tobacco Association,2011:37-50.

Included in

Food Science Commons



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.