Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes

Addiction. 2016 Mar;111(3):535-44. doi: 10.1111/add.13183. Epub 2015 Nov 11.


Aims: To measure the systemic retention of nicotine, propylene glycol (PG) and vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics.

Design: E-cigarette users recruited over the internet participated in a 1-day research ward study. Subjects took 15 puffs from their usual brand of e-cigarette. Exhaled breath was trapped in gas-washing bottles and blood was sampled before and several times after use.

Setting: San Francisco, California, USA.

Participants: Thirteen healthy, experienced adult e-cigarette users (six females and seven males).

Measurements: Plasma nicotine was analyzed by gas chromatography-mass spectrometry (GC-MS/MS) and nicotine, VG and PG in e-liquids and gas traps were analyzed by LC-MS/MS. Heart rate changes and subjective effects were assessed.

Findings: E-cigarettes delivered an average of 1.33 (0.87-1.79) mg [mean and 95% confidence interval (CI)] of nicotine, and 93.8% of the inhaled dose, 1.22 (0.80-1.66) was systemically retained. Average maximum plasma nicotine concentration (Cmax ) was 8.4 (5.4-11.5) ng/ml and time of maximal concentration (Tmax ) was 2-5 minutes. One participant had Tmax of 30 minutes. 84.4% and 91.7% of VG and PG, respectively, was systemically retained. Heart rate increased by an average of 8.0 beats per minute after 5 minutes. Withdrawal and urge to smoke decreased and the e-cigarettes were described as satisfying.

Conclusions: E-cigarettes can deliver levels of nicotine that are comparable to or higher than typical tobacco cigarettes, with similar systemic retention. Although the average maximum plasma nicotine concentration in experienced e-cigarette users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential.

Keywords: Abuse liability; addiction; e-cigarette; nicotine pharmacokinetics; nicotine retention; propylene glycol; vegetable glycerin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Breath Tests
  • Chromatography, Liquid
  • Electronic Nicotine Delivery Systems*
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Glycerol / administration & dosage*
  • Glycerol / metabolism
  • Humans
  • Male
  • Middle Aged
  • Nicotine / administration & dosage*
  • Nicotine / metabolism
  • Nicotine / pharmacokinetics
  • Nicotinic Agonists / administration & dosage*
  • Nicotinic Agonists / pharmacokinetics
  • Propylene Glycol / administration & dosage*
  • Propylene Glycol / metabolism
  • Solvents / administration & dosage*
  • Solvents / metabolism
  • Tandem Mass Spectrometry
  • Young Adult


  • Nicotinic Agonists
  • Solvents
  • Propylene Glycol
  • Nicotine
  • Glycerol