Liquid chromatography with tandem mass spectrometry method for the determination of nicotine and minor tobacco alkaloids in electronic cigarette refill liquids and second-hand generated aerosol

J Sep Sci. 2017 Mar;40(5):1049-1056. doi: 10.1002/jssc.201601076. Epub 2017 Jan 31.


A liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of nicotine and seven minor tobacco alkaloids in both refill liquids for electronic cigarettes and their generated aerosol was developed and validated. The limit of detection and limit of quantification values were 0.3-20.0 and 1.0-31.8 ng/mL, respectively. Within-laboratory reproducibility was 8.2-14.2% at limit of quantification values and 4.8-12.7% at other concentration levels. Interday recovery was 75.8-116.4%. The method was applied to evaluate the compliance of commercial liquids (n = 95) with their labels and to assess levels of minor alkaloids. Levels of nicotine and its corresponding compounds were also evaluated in generated aerosol. About 47% of samples showed differences above ±10 % of the stated nicotine concentration. About 78% of the "zero nicotine" liquids showed traces in the range of 1.3 ± 0.1-254.0 ± 14.6 μg/mL. Nicotine-N'-oxides, myosmine, and anatabine were the most common minor alkaloids in liquids containing nicotine. Nicotine and N'-oxides were detected in all air samples when aerosol was generated from liquids containing nicotine. Nicotine average emissions from electronic cigarette (2.7 ± 0.9 μg/m3 ) were significantly lower (p < 0.01, t-test) with respect to conventional cigarette (30.2 ± 1.5 μg/m3 ).

Keywords: aerosols; electronic cigarettes; liquid chromatography; refill liquids; tobacco alkaloids.

MeSH terms

  • Aerosols / analysis
  • Alkaloids / analysis*
  • Chromatography, Liquid*
  • Electronic Nicotine Delivery Systems*
  • Nicotiana / chemistry
  • Nicotine / analysis*
  • Reproducibility of Results
  • Tandem Mass Spectrometry*


  • Aerosols
  • Alkaloids
  • Nicotine