Content uploaded by Leon Kośmider
Author content
All content in this area was uploaded by Leon Kośmider on Jan 10, 2017
Content may be subject to copyright.
Nicotine & Tobacco Research
1
doi: 10.1093/ntr/nts103
© The Author 2012. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.
All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
small kiosks in shopping malls. ECs were developed in 2004 in
China, who remains the main manufacturer of these devices.
ECs have not been manufactured by any tobacco or pharmaceuti-
cal companies and as a consumer product were not tested and
approved by regulatory agencies (e.g., U.S. Food and Drug Agency
(FDA), U.K. Medicines and Healthcare Products Regulatory
Agency [MHRA]) before their introduction to the global market
(Trtchounian & Talbot, 2010).
Each EC contains a: (a) cartridge(s) (CA) that contains nicotine
solution in propylene glycol or glycerin, (b) heating element to
vaporize the nicotine solution, (c) microprocessor with a sensor
that activates the heating element when the EC is puffed, (d)
rechargeable battery, and sometimes (e) LED diode that imitates
the glow of a burning cigarette cone. The principle of the EC is to
deliver nicotine in a form of aerosol that does not contain any
tobacco specific toxins. It is puffed in a similar way to a regular
cigarette. When a sensor detects airflow, it activates a heating
element that is in a contact with the cartridge containing nicotine
solution. As a result of increased temperature and airflow, nicotine
is vaporized and an aerosol with droplets of solution is generated
and inhaled by the EC user (Cahn & Siegel, 2010; Etter, Bullen,
Flouris, Laugesen, & Eissenberg, 2011; Henningfield & Zaatari,
2010; Pauly, Li, & Barry, 2007; Wollscheid & Kremzner, 2009).
The most common solvents for nicotine are propylene glycol
and glycerin, as when heated they form an aerosol that closely
imitates cigarette smoke. The other components of the solution
include water, ethanol, and various additives but these can
differ in presence and proportion between EC brands. Cartridges
are available in various flavors such as tobacco, menthol,
strawberry, apple, chocolate, vanilla, and many others. They are
usually labeled according to their nicotine content as “extra
strong/very high,” “strong/high,” “regular/medium,” “light/
low,” “ultra light/very low,” or “zero/no nicotine” if they
are nicotine free. The nicotine content is determined by the
manufacturers and often varies between brands and within a
brand’s models. Some types of EC cartridges, commonly called
“cartomizers” or “atomized cartridges”, contain a built-in heating
element and others can be refillable by the user with ready-to-
use nicotine refill solutions (RS), commonly called “liquids,”
“e-liquids,” or “juices.” The latter are more popular among
Abstract
Introduction: The electronic cigarette (EC) is a plastic device
that imitates conventional cigarettes and was developed to
deliver nicotine in a toxin-free vapor. Nicotine in a solution is
heated and vaporized when a person puffs through the device
and is inhaled as a vapor into the mouth. The EC is a new product
on the market and little is known about its safety and nicotine
delivery efficacy. The aim of the study was to analyze nicotine
levels in vapor generated from various EC brands and models.
The study was designed to assess efficacy and consistency of
various ECs in converting nicotine to vapor and to analyze
dynamics of nicotine vaporization.
Methods: Sixteen ECs were selected based on their popularity in
the Polish, U.K. and U.S. markets. Vapors were generated using
an automatic smoking machine modified to simulate puffing con-
ditions of real EC users. Nicotine was absorbed in a set of washing
bottles with methanol and analyzed with gas chromatography.
Results: The total level of nicotine in vapor generated by 20
series of 15 puffs varied from 0.5 to 15.4 mg. Most of the
analyzed ECs effectively delivered nicotine during the first 150–180
puffs. On an average, 50%–60% of nicotine from a cartridge was
vaporized.
Conclusions: ECs generate vapor that contains nicotine, but
EC brands and models differ in their efficacy and consistency of
nicotine vaporization. In ECs, which vaporize nicotine effec-
tively, the amount inhaled from 15 puffs is lower compared with
smoking a conventional cigarette.
Introduction
The electronic nicotine delivery system, commonly called elec-
tronic cigarette or e-cigarette (EC), is a plastic device that was
designed to imitate a regular cigarette and to deliver a nicotine-
containing aerosol when puffed by the user. ECs have gained
popularity around the world. They are mostly promoted via
the Internet but recently also by the entertainment industry.
They are available through online stores or retail outlets such as
Original Investigation
Nicotine Levels in Electronic Cigarettes
Maciej L. Goniewicz, Ph.D.,1,2 Tomasz Kuma, M.Pharm.,1 Michal Gawron, M.Pharm.,1 Jakub Knysak, M.Pharm.,1 &
Leon Kosmider, M.Pharm.1
1 Department of General and Analytical Chemistry, School of Pharmacy and Laboratory Medicine, Medical University of Silesia,
Sosnowiec, Poland
2 Tobacco Dependence Research Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, United Kingdom
Corresponding Author: Maciej L. Goniewicz, Ph.D., Tobacco Dependence Research Unit, Bart’s and the London School of Medicine
and Dentistry, Wolfson Institute of Preventive Medicine, Queen Mary University of London, 55 Philpot Street, London E1 2JH,
United Kingdom. Telephone: +44-20-7882-8244; Fax: +44-20-7377-7237; E-mail: m.goniewicz@qmul.ac.uk
Received October 28, 2011; accepted March 6, 2012
Nicotine & Tobacco Research Advance Access published April 22, 2012
at Society for Research on Nicotine and Tobacco member access on April 25, 2012http://ntr.oxfordjournals.org/Downloaded from
2
Nicotine levels in electronic cigarettes
some users since their use is more cost-effective than nonrefillable
cartridges. These solutions are also available in a similar range of
flavors and concentrations of nicotine.
There is some inconsistency in existing data regarding the
efficacy of ECs as nicotine delivery devices. The U.S. FDA evalu-
ated two brands of EC for nicotine content. Nicotine was
detected in both products for all cartridges labeled as containing
low, medium, and high levels of nicotine. The sparging apparatus
was used to quantify the amount of nicotine released during use
of these devices. Levels found were consistent with the labeling
(low, medium, and high); however, the cartridge labeled “no
nicotine” still delivered some nicotine (Westenberger, 2009).
Another study also found nicotine in cartridges labeled as
containing no nicotine (Hadwiger et al., 2010).
Although nicotine seems to be present in ECs, it might not
be delivered effectively to the blood stream. Three human stud-
ies found no or negligible increases in nicotine blood levels after
acute use of EC in naïve users, but it has been also shown that
using some brands of EC alleviates nicotine craving (Bullen
et al. 2010; Eissenberg, 2010; Vansickel, Cobb, Weaver, &
Eissenberg, 2010). One study found substantial amounts of
cotinine, a metabolite of nicotine, in the saliva of EC users
suggesting that experience with the device is likely to influence
blood nicotine levels (Etter & Bullen, 2011).
There are at least three important factors that determine the
efficacy of nicotine delivery from EC to the body. The first is the
nicotine content of a cartridge. Puffing an EC with high nicotine
levels should lead to inhalation of higher doses of the drug.
Second is the efficacy of the vaporization process that deter-
mines how much nicotine is actually transferred from a cartridge
into the aerosol. Finally, bioavailability of nicotine from the EC
aerosol is a key factor, since it limits the amount of inhaled
nicotine that is absorbed into the blood stream and reaches the
nicotinic receptors in the brain. This study was designed to
explore the first two of the above factors by measuring nico-
tine levels in cartridges and refill solutions and evaluating the
nicotine vaporization efficacy of various models of EC brands.
Materials and Methods
EC, Cartridges, and Nicotine Refill
Solutions
We decided to study the most popular brands of ECs available
in domestic, European, and U.S. markets. Since the Internet
seems to be the main distribution channel for these products,
we browsed google.com and google.pl web search engines, price
comparison websites, online marketplaces, and Internet discus-
sion forums for EC users and identified 30 popular brands of
ECs. We ranked them based on numbers of records in web
search engines and chose the 15 brands with the highest number
of records. Only one model was chosen per brand, except for the
brand Janty, for which we decided to test two popular models
(eGo and Dura). The characteristics of ECs evaluated in the
study are provided in Table 1, and all products are presented in
Supplementary Figure 1.
All products were purchased from commercial sources.
Eleven ECs were purchased from Polish online shops, four from
U.K.-based services, and one from a U.S. online shop. All brand
names were removed from the products, and each product was ran-
domly assigned a code to blind lab technicians to the brand tested.
Cartridges and refill solutions were purchased from the
same sources to ensure they were compatible with tested ECs. In
order to achieve variability of the products, we decided to test
20 cartridges and 15 nicotine refill solutions. Since they came
with various strengths and aromas, there were additional car-
tridges and refill solution that were not part of the 16 chosen
ECs. Characteristics of cartridges and nicotine refill solutions
evaluated in the study are provided in Table 2, and all cartridges
are presented in Supplementary Figure 2.
We paired each tested EC with cartridges of the same brand
name and from the same batch and series, that is, the cartridges
were from the same packaging box of the same brand and model
and have the same nicotine content and flavor according to
their manufacturer. Total of six cartridges were used for test,
three unused cartridges were used to measure nicotine content
and three original cartridges were used for EC testing.
Nicotine Aerosol Generation From EC
Aerosol from ECs was generated using smoking machine
“Palaczbot” (Technical University of Lodz, Poland) designed
for the purpose of this study. This is a one-port linear piston-
like smoking machine with adjustable puffing regimes in a very
wide range, controlled by computer software. Test conditions
were determined to reflect real-life puffing patterns of EC users.
We recruited 10 volunteers (aged 35 ± 20 years, 8 males) who
used various brands and models of EC for at least one month and
measured their puffing topography with modified and calibrated
CressMicro monitors (Borgwaldt Ltd., Germany). The average
puffing topography was as follows (M ± SD): puff duration
of 1.8 ± 0.9 s, intervals between puffs of 10 ± 13 s, puff volume
70 ± 68 ml, and number of puffs taken in one puffing session
was 15 ± 6. All testing procedures in this work were carried out
using the same averaged puffing conditions. A total of 300 puffs
were taken from each EC in 20 series of 15 puffs with intervals
between series of 5 min each. Each EC was tested three times on
3 following days after batteries were recharged during nights.
Nicotine Analysis in EC Aerosol
Nicotine from EC aerosol was absorbed using liquid extraction to
organic solvent technique. EC was connected with short Teflon
pipes with a set of two 200-ml gas washing bottles with coarse
spargers. Each washing bottle contained 50 ml of methanol with
quinoline as an internal standard (10 mg/ml). Both washing bottles
were immersed in acetone–dry ice bath in order to avoid any
losses of volatile solvent. A picture of set for vapor generation from
EC and nicotine absorption is presented in Supplementary Figure 3.
Samples of 0.25 ml were collected from each washing bottle
every 15 puffs, with a total of 150 puffs, and every 30 puffs with
a total of 300 puffs. A total of 30 samples were collected during
each testing procedure for each EC.
Nicotine was analyzed using gas chromatography method with
Thermionic Specific Detector (GC-TSD, Varian Inc.). We modi-
fied the standard NIOSH 2551 method for determination of nico-
tine in air (National Institute for Occupational Safety and Health,
1998). CP-Sil 8CB, 25 m × 0.25 mm × 0.39 mm (1.2 mm; Varian
at Society for Research on Nicotine and Tobacco member access on April 25, 2012http://ntr.oxfordjournals.org/Downloaded from
3
Nicotine & Tobacco Research
Table 1. Nicotine Amounts in Original Cartridges and Estimated Levels Delivered to Vapor With 150 and 300 Puffs by Analyzed
Electronic Cigarettes
EC code Brand name Model Retailer Country
Source of
product
Cartridge
(Table 2)
Nicotine amounts
in original unused
cartridges (mg, %)
Nicotine levels released to vapor from cartridge
Estimated based
on its analysis in
vapor (mg)
Estimated based on
its analysis in used
cartridges (mg)a
With 150 puffs (%) With 300 puffs (%) With 300 puffs (%)
EC 01 Joye 510 Inspired s.c. Poland Online CA 11 4.2 ± 0.0 (100) 1.7 ± 0.6 (40) 1.8 ± 0.1 (43) 1.8 ± 0.2 (43)
EC 02 Janty eGo Janty Poland Online CA 04 4.7 ± 0.3 (100) 2.6 ± 0.3 (55) 2.8 ± 0.2 (60) 3.2 ± 0.1 (75)
EC 03 Janty Dura Janty Poland Online CA 04 4.7 ± 0.3 (100) 2.4 ± 0.7 (51) 2.8 ± 0.8 (60) 2.7 ± 0.2 (57)
EC 04 DSE 901 Farsee Poland Online CA 15 9.4 ± 0.8 (100) 2.2 ± 0.6 (23) 2.5 ± 0.4 (27) 3.3 ± 0.7 (35)
EC 05 Trendy 808 Damhess Poland Online CA 08 1.6 ± 0.2 (100) 0.3 ± 0.2 (19) 0.5 ± 0.1 (31) 1.1 ± 0.1 (68)
EC 06 Nicore M401 Atina Poland Poland Online CA 10 4.9 ± 0.3 (100) 1.9 ± 0.3 (39) 2.3 ± 0.5 (47) 3.0 ± 0.9 (61)
EC 07 Mild 201 Mild Poland Online CA 07 19 ± 0.5 (100) 8.4 ± 1.1 (44) 8.8 ± 1.6 (46) 14 ± 0.8 (77)
EC 08 Colinss Age Colinss Poland Kiosk CA 06 11 ± 1.5 (100) 4.7 ± 1.0 (43) 7.2 ± 1.0 (65) 6.3 ± 0.6 (57)
EC 09 Premium PR111 Premium Poland Online CA 09 12 ± 0.7 (100) 5.1 ± 1.1 (43) 7.4 ± 0.6 (61) 8.2 ± 0.9 (68)
EC 10 Ecis 510 Arcotech Poland Online CA 12 4.9 ± 0.3 (100) 2.6 ± 0.4 (53) 3.1 ± 0.7 (63) 4.0 ± 0.2 (81)
EC 11 Dekang Pen Ecigars Polska Poland Kiosk CA 01 18 ± 0.8 (100) 8.7 ± 1.0 (48) 15.4 ± 2.1 (85) 14 ± 0.8 (74)
EC 12 Intellicig Evolution Intellicig United Kingdom Online CA 16 8.0 ± 0.9 (100) 1.6 ± 0.2 (20) 2.3 ± 0.1 (29) 2.4 ± 0.2 (30)
EC 13 SkyCig SkyCig SkyCig United Kingdom Online CA 17 12 ± 0.1 (100) 2.3 ± 0.8 (19) 2.5 ± 0.4 (21) 2.5 ± 0.4 (21)
EC 14 Liberro Black LiberroLtd United Kingdom Online CA 18 19 ± 0.5 (100) 6.1 ± 0.9 (32) 11.2 ± 1.1 (59) 10 ± 1.3 (55)
EC 15 Njoy NPro NJoy United States Online CA 19 16 ± 0.3 (100) 5.0 ± 1.7 (31) 7.5 ± 2.4 (47) 8.9 ± 2.4 (56)
EC 16 Gamucci 110228 GamucciLtd United Kingdom Online CA 20 15 ± 0.2 (100) 8.1 ± −0.1 (54) 10.7 ± 0.5 (71) 12 ± 0.4 (78)
Note. All results are M ± SE (n = 3). Values in brackets are percentages of nicotine levels measured in original unused cartridges.
aLevels of nicotine released with 300 puffs were calculated as differences between mean amount of nicotine in original cartridges of the same type and brand and nicotine amounts in used cartridges removed
from EC after 300 puffs.
at Society for Research on Nicotine and Tobacco member access on April 25, 2012http://ntr.oxfordjournals.org/Downloaded from
4
Nicotine levels in electronic cigarettes
Inc.) capillary column with flow rate of helium of 2.4 ml/min
were used. Temperature of injector and detector was 300 °C,
column temperature increased from 60 to 200 °C (20 °C/min)
and hold for 5 min. Injection volume was 1 ml, and quinoline
was used as an internal standard. Calibration curve was gener-
ated to cover the range of nicotine concentration from 0.5 to 50
mg/ml, which corresponds to cumulative nicotine levels in EC
aerosol from 0.2 to 20 mg. The method was validated as per the
International Conference on Harmonization guideline Q2 (R1;
ICH, 2005). Precision of the method was 18%, and quantitation
limit was 0.05 mg/ml. Exemplary chromatogram of the analyzed
sample is presented in Supplementary Figure 4.
Nicotine Analysis in Cartridges and Refill
Solutions
Nicotine was analyzed in three cartridges of the same batch and
series, taken from one box of each brand included in the study.
Moreover, nicotine was also analyzed in used cartridges after
300 puffs were taken in the experiments described above. Know-
ing the amounts of nicotine in the original and used cartridges,
it was possible to estimate how much nicotine was released to
vapor. Measured amounts of nicotine in original/unused
cartridges were also compared with values declared by manu-
facturers and retailers on their packages.
Table 2. Results of Nicotine Analysis in Original Cartridges and Refill Solutions
Product code Brand name Model/flavor Retailer Country
Source of
product
Labeled
nicotine
concentration
(mg)
Determined
nicotine
concentration
(mg)a
Relative
difference in
concentration
(%) p Valueb
Cartridges
CA 01 SGC Regular Ecigars Polska Poland Online 18 18 ± 0.8 0 .6159
CA 02 n/a Tabaco n/a Poland Kiosk 16 14 ± 1.2 −12 .0362
CA 03 Colinss Tabaco Colinss Poland Online 18 13 ± 1.0 −28 .0008
CA 04 Janty Marlboro Janty Poland Online 16 5 ± 0.3 −69 .0000
CA 05 n/a Tobacco n/a Poland Kiosk 0 0 ± 0.0 0 .0000
CA 06 Colinss Camel Colinss Poland Online 18 11 ± 1.5 −39 .0012
CA 07 Mild Marlboro Mild Poland Online 18 19 ± 0.5 6 .1047
CA 08 Trendy Trendy Damhess Poland Online 18 2 ± 0.2 −89 .0000
CA 09 Premium Tabacco Premium Poland Online 16 12 ± 0.7 −25 .0013
CA 10 Nicore Marlboro AtinaPoland Poland Online 18 5 ± 0.3 −72 .0000
CA 11 n/a Marlboro n/a Poland Kiosk 4 4 ± 0.0 0 .0000
CA 12 Ecis Mentol Arcotech Poland Online 11 5 ± 0.3 −55 .0000
CA 13 Mini Regular n/a Poland Kiosk 4 5 ± 0.2 25 .0010
CA 14 Mini Regular n/a Poland Kiosk 0 0.3 ± 0.0 0 .0000
CA 15 Mini Regular Farsee Poland Online 16 9 ± 0.8 −44 .0002
CA 16 Intellicig Regular Intellicig UK Online 8 8 ± 0.9 0 .6192
CA 17 SkyCig Regular SkyCig UK Online 12 12 ± 0.1 0 .0000
CA 18 Liberro Classic Liberro Ltd. UK Online 18 19 ± 0.5 6 .0605
CA 19 NPro Regular Njoy USA Online 18 16 ± 0.3 −11 .0009
CA 20 Gamucci Regular Gamucci UK Online 16 15 ± 0.2 −6 .0020
Refill solutions
RS 01 Dekang Fortune Strike Ecigars Polska Poland Online 14 14 ± 0.7 0 .6199
RS 02 Red USA Mix Inspired s.c. Poland Online 24 19 ± 0.3 −21 .0000
RS 03 Colinss Camel Colinss Poland Online 18 16 ± 0.7 −11 .0056
RS 04 Ecis High Marlbo ECIS-shop.eu Poland Online 16 18 ± 1.3 11 .0725
RS 05 Extreme Standard H Dami PHPU Poland Kiosk 16 15 ± 0.5 −6 0362
RS 06 Virginia n/a Dami PHPU Poland Kiosk 18 16 ± 1.4 11 .8084
RS 07 n/a Mint Medium n/a Poland Kiosk 11 10 ± 0.8 −9 .2262
RS 08 n/a MintVery High n/a Poland Kiosk 24 21 ± 1.1 −13 .1216
RS 09 Ecigar.pl Regular Ecigars Polska Poland Online 24 25 ± 1.1 4 .1331
RS 10 Mild Tabacco Chic Poland Online 18 18 ± 1.4 0 .9291
RS 11 Janty TXS-Z Texas Janty Poland Online 0 0 ± 0.0 0 .0000
RS 12 Janty TXS-H Texas Janty Poland Online 16 16 ± 0.3 0 .5329
RS 13 Janty Mint-H Janty Poland Online 16 4 ± 0.1 −75 .0000
RS 14 Nicore Liquid Atina Poland Poland Online 18 23 ± 2.4 28 .0029
RS 15 EssentialOil Virginia Tabacco n/a Poland Online 12 14 ± 0.4 17 .0015
Note. aMean ± SE.
bOne-sample t test. n/a=not available (information not indicated directly on packages).
at Society for Research on Nicotine and Tobacco member access on April 25, 2012http://ntr.oxfordjournals.org/Downloaded from
5
Nicotine & Tobacco Research
After gently removing a cartridge from its package, it was
placed in a glass 200-ml flask and 50 ml of ethyl acetate was
added along with 100-ml internal standard solution (quinoline
50 mg/ml in methanol). The flask was covered with parafilm
and placed in an ultrasound bath. After 30 min, 1 ml of the
extract was collected and analyzed with the chromatography
method described above. Three cartridges of each model were
tested. Calibration solutions of nicotine in propylene glycol
with a concentration range of 0.01–40 mg/ml were prepared
by weighting proper nicotine amounts and dissolving them in
solvent. Calibration and control cartridges were prepared by
spiking empty cartridges with 0.5 ml of calibration solution.
The whole analytical procedure was then performed to calibrate
and validate the method (ICH, 2005). Precision of the method was
15%, recovery of 98%, and quantitation limit was 0.1 mg/cartridge.
In order to analyze nicotine in refill solutions, samples
of 100 ml of each examined solution were diluted with 10 ml
methanol, and after adding internal standard (100 ml quinoline
solution 50mg/ml in methanol), were vigorously shaken for
10 min and analyzed as described above. Three samples of each
refill solution model were tested. To calibrate and validate the
method, the same nicotine solutions as described above for the
cartridges procedure were used. Precision of the method was
17%, recovery of 102%, and quantitation limit was 0.05 mg/ml.
Statistical Analysis
For each analyzed EC, a nicotine delivery profile was generated.
The profiles represent the relationship between cumulative dose
of nicotine released from a cartridge to aerosol and number of
puffs. Each point represents M values from three test runs
whereas bars correspond to the values of SEs. Differences in
nicotine amounts released to aerosol among analyzed ECs
were compared using nonparametric ANOVA with Tukey test
for comparisons. Measured amounts of nicotine in original
cartridges were compared with values declared on their pack-
ages using one-sample t test. For all tests Statistica 6.0 (Statsoft)
software was used.
Results
Levels of Nicotine in EC Aerosol
Aerosol was visibly being produced during the full 300 puffs
taken from each product tested. Results are presented as abso-
lute values in mg of nicotine but also as percentages of nicotine
levels measured in original unused cartridges. Absolute and
relative levels of nicotine released with 150 and 300 puffs of the
examined ECs are summarized in Table 1. Absolute and relative
levels of nicotine released with 300 puffs were also calculated as
differences between mean nicotine amount in original unused
cartridges of the same brand and model and amounts that
remained in the cartridge after 300 puffs. Delivery profiles of
nicotine from cartridges to vapor for each analyzed ECs are
presented in Figure 1.
Levels of nicotine in vapors released from analyzed ECs with
150 puffs varied from 0.3 ± 0.2 (EC 05) to 8.7 ± 1.0 mg (EC 11) and
with 300 puffs from 0.5 ± 0.1 (EC 05) to 15.4 ± 2.1 (EC 11; Table 1).
Analyzed ECs varied in efficacy and consistency of nicotine
vaporization (p < .05). For example, EC 11 and EC 16 vaporized
nicotine with 300 puffs with a high efficacy of 85% and 71%,
respectively (Table 1). EC 08, 09, 11, 14, and 16 delivered nico-
tine from cartridges to vapor consistently throughout 300 puffs
(short bars on nicotine delivery profiles represent low standard
error [SE] values; Figure 1). Contrarily, EC 05 was characterized
by very low consistency and was very ineffective in nicotine
vaporization, delivering to vapor only 31% of the nicotine present
in the cartridge (Table 1).
Levels of Nicotine in Original Cartridges
and Refill Solutions
Results of the tested cartridges and refill nicotine solutions for
nicotine content are presented in Table 2. We found that nico-
tine amounts in 9 out of 20 of the analyzed cartridges differed by
more than 20% from values declared by their manufacturers
(CA 03, 04, 06, 08, 09, 10, 12, 13, and 15). The differences of the
same magnitude were detected among 3 out of 15 nicotine refill
solutions (RS 02, 13, and 14). For some brands, declared
amounts of nicotine were the same as those analyzed by us,
indicating the manufacturer’s credibility.
Discussion
Electronic cigarettes are new products available on international
markets. They differ not only by brand names, models, and
designs but also by technical characteristics. There has not been
any comprehensive testing of various brands and models to see
how they differ between each other in nicotine delivery. In our
study, we analyzed 16 various EC models, chosen based on their
popularity, to see if the products effectively exposed their users
to significant amounts of nicotine.
There have been some preliminary studies indicating that
ECs may expose their users to nicotine. In most of the studies,
nicotine was found in cartridge and refill solutions but there is
no data so far if any nicotine is actually effectively vaporized
(Coulson, 2009; Ellicott, 2009; Exponent, 2009; Kieckbush,
2009, 2010; Laugesen, 2008, 2010; Valance & Ellicot, 2008;
Westenberger 2009). Three published studies with human sub-
jects who used one of the products showed little or no delivery
of nicotine to the blood stream, even when products that con-
tained high nicotine levels were used (Bullen et al., 2010;
Eissenberg, 2010; Vansickel, Cobb, Weaver, & Eissenberg,
2010). One potential factor affecting this might be poor nicotine
delivery from cartridges to vapors, resulting in low nicotine levels
inhaled by studied subjects.
Based on our preliminary observations, we decided to test
products with conditions, which closely reflect how experienced
“EC smokers” use their products. We tested each product using
20 series of 15 puffs. We found that 300 puffs of ECs that con-
tained “high nicotine” cartridges delivered between 0.5 and 15.4
mg of nicotine, whereas EC with cartridges labeled as “low” or
“medium” delivered between 0.5 and 3.1 mg of the drug. The
efficacy of nicotine vaporization differed across ECs. Evaluated
ECs vaporized 21% to 85% of relative amounts of nicotine
present in the cartridges. The high variability in performance
properties of ECs was recently reported by Trtchounian, Williams,
and Talbot (2010). They found that EC brands produced aerosols,
which varied in density from puff to puff. Our findings seem to
at Society for Research on Nicotine and Tobacco member access on April 25, 2012http://ntr.oxfordjournals.org/Downloaded from
8
Nicotine levels in electronic cigarettes
confirm their hypothesis about not uniform nicotine delivery
from ECs.
Nicotine levels from a single puff of 70 ml may be estimated
to be between 1.7 and 51.3 mg. Results of repeated testing of ECs
with three different cartridges with the same label (menthol
high) by the FDA gave varying results from 26.8 to 43.2 mg nico-
tine per 100 ml puff, which is close to the upper levels observed
in the present study (Westenberger, 2009). Despite the fact that
we tested products with lower puff volumes than in the FDA
study (70 vs. 100 ml), we found high consistency between the
results of one product tested in both studies (EC15; 5.0 vs. 5.3 mg
nicotine per 150 puffs).
Assuming a series of 15 puffs is equivalent to smoking one
cigarette; this allows us to make some dose comparisons. One
series of 15 puffs might have delivered 0.025–0.77 mg nicotine,
which is lower than a dose inhaled from one smoked tobacco ciga-
rette (from 1.54 to 2.60 mg; Djordjevic, Stellman, & Zang, 2000).
By systematically analyzing how much of the nicotine was
released from an EC with every 15 puffs, we were able to generate
a nicotine delivery profile for each tested product. Analysis of
the profiles indicates that only part of the nicotine present in a
cartridge is vaporized and only some of the nicotine from
cartridge is inhaled by EC users (on average 50%–60%). Thus,
making conclusions on how much nicotine is inhaled by EC
users based on the content in cartridges might lead to overesti-
mation of the effective dose. Improvement of the vaporization
efficacy would make more or even all the nicotine present in a
cartridge available for EC users.
Moreover, nicotine delivery profiles provided interesting
data on efficacy of the vaporization process, indicating that
most of the nicotine is delivered during the first 150–180 puffs.
Based on this finding, potential users of the products should be
instructed to replace nicotine cartridge every 150 puffs in order
to achieve effective and steady nicotine exposure.
Our results also suggest that some products are inconsistent
in delivering nicotine. These products might deliver different
levels of nicotine to their users each time they are used even if
containing cartridges of the same nicotine content. This finding
is consistent with the results found in a study by Williams and
Talbot (2011). The authors reported that the ECs they tested lasted
for a variable number of puffs, and some variation was found in
models within a brand, when different cartridges were used.
We also found significant differences between labeled and
true levels of nicotine in cartridges and refill solutions. Traces of
nicotine were also detected in one of two cartridges labeled as
containing no nicotine. These findings indicate that informa-
tion about nicotine levels provided on product packages may
be misleading to customers. In order to sell the best quality
products to customers, manufacturers of ECs should develop
and implement quality standards for their products and follow
good manufacture policy. The authority to independent agencies
should be given to control quality of the products available on
market.
We presented a preliminary evaluation of 16 ECs, 20 car-
tridges, and 15 refill solutions and our study was not intended to
provide an accurate characterization of any particular brand.
There are many potential limitations in the generality and
reliability of our findings because of a relatively small number
of samples from each product. Further research is needed to
investigate if the variability in nicotine delivery is primarily due
to brand variability or a combination of brand variability and
fluctuation within brands.
Our study reflects the early stage of objective research on
ECs and raises new questions. First, how high might nicotine
levels be if users were instructed to puff them as hard as possi-
ble? Puff duration for individuals using ECs in YouTube videos
was longer than we used in the study to simulate EC use with
smoking machine (4.3 vs. 1.8 s; Hua, Yip, & Talbot, 2011).
Longer puff duration may help EC users compensate for the
poor delivery of nicotine from ECs. Second, what is the prime
site of nicotine absorption from EC? Does nicotine from EC
reach blood stream via buccal mucosa only? or is there any lung
absorption? Substantial amounts of cotinine, a metabolite of
nicotine, found in the saliva of EC users suggest that experience
with the device is likely to influence blood nicotine levels (Etter &
Bullen, 2011). Finally, can ECs produce the arterial plasma
spikes reflecting substantial lung delivery as have been shown
with tobacco cigarettes?
Supplementary Material
Supplementary Figures 1–4 can be found online at http://www.
ntr.oxfordjournals.org
Funding
This work was supported by the Ministry of Science and Higher
Education of Poland (grant number N N404 025638). The study
sponsor had no involvement in the study design, collection,
analysis, and interpretation of data, the writing of the manu-
script or the decision to submit the manuscript for publication.
MLG is currently funded by the U.K. Center for Tobacco Con-
trol Studies, U.K. Public Health Centre of Excellence (UKCTCS).
UKCTCS receives it funding from the Economic and Social
Research Council, British Heart Foundation, Cancer Research
U.K., National Institute for Health Research, and Medical
Research Council.
Declaration of Interests
MLG received research funding from Pfizer, manufacturer of stop
smoking medication.
Acknowledgments
We thank Karol Kubicki, Piotr Giza, and Piotr Kobialka,
students of biotechnology at School of Pharmacy and Laboratory
Medicine, Medical University of Silesia, Poland, for their help
in the laboratory.
References
Bullen, C., McRobbie, H., Thornley, S., Glover, M., Lin, R., &
Laugesen, M. (2010). Effect of an electronic nicotine delivery
at Society for Research on Nicotine and Tobacco member access on April 25, 2012http://ntr.oxfordjournals.org/Downloaded from
9
Nicotine & Tobacco Research
device (e-cigarette) on desire to smoke and withdrawal, user
preferences and nicotine delivery: Randomised cross-over trial.
Tobacco Control, 19, 98–103. doi:10.1136/tc.2009.031567
Cahn, Z., & Siegel, M. (2010). Electronic cigarettes as a harm
reduction strategy for tobacco control: A step forward or a
repeat of past mistakes? Journal of Public Health Policy, 32, 16–
31. doi:10.1057/jphp.2010.41
Coulson, H. (2009). Analysis of components from Gamucci
electronic cigarette cartridges, tobacco flavour regular smoking liquid.
Retrieved from http://truthaboutecigs.com/science/7.pdf
Djordjevic, M., Stellman, S. D., & Zang, E. (2000). Doses of
nicotine and lung carcinogens delivered to cigarette smokers.
Journal of the National Cancer Institute, 92, 106–111. doi:10.1093/
jnci/92.2.106
Eissenberg, T. (2010). Electronic nicotine delivery devices:
Ineffective nicotine delivery and craving suppression after acute
administration. Tobacco Control, 19, 87–88. doi:10.1136/
tc.209.033498
Ellicott, M. (2009). Analysis of components from “e-Juice XX
HIGH 36 mg/ml rated nicotine solution” ref S 55434. Retrieved
from http://truthaboutecigs.com/science/11.pdf
Etter, J. F., & Bullen, C. (2011). Saliva cotinine levels in users
of electronic cigarettes. European Respiratory Journal, 38, 1219–
1220. doi:10.1183/09031936
Etter, J. F., Bullen, C., Flouris, A. D., Laugesen, M., &
Eissenberg, T. (2011). Electronic nicotine delivery systems: A
research agenda. Tobacco Control, 20, 243–248. doi:10.1136/
tc.2010.042168
Exponent. (2009). NJOY e-cigarette health risk assessment.
Retrieved from http://truthaboutecigs.com/science/5.php
Hadwiger, M. E., Trehy, M. L., Ye, W., Moore, T., Allgire, J., &
Westenberger, B. (2010). Identification of amino-tadalafil and
rimonabant in electronic cigarette products using high pressure
liquid chromatography with diode array and tandem mass spec-
trometric detection. Journal of Chromatography A, 48, 7547–
7555. doi:10.1016/j.chroma.2010.10.018
Henningfield, J., & Zaatari, G. (2010). Electronic nicotine delivery
systems: Emerging science foundation for policy. Tobacco Control,
19, 89–90. doi:10.1136/tc.2009.035279
Hua, M., Yip, H., & Talbot, P. (2011). Mining data of usage of
electronic nicotine delivery systems (ENDS) from YouTube
videos. Tobacco Control, Advanced Access published online.
doi:10.1136/tobaccocontrol-2011-050226
International Conference on Harmonization. (2005). Technical
requirements for registration of pharmaceuticals for human use,
Topic Q2 (R1): Validation of analytical procedures: Text and
Methodology. Geneva, Switzerland. Retrieved from http://www.
ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/
Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf
Kieckbush, R. (2009). Characterization of liquid “Smoke Juice”
for electronic cigarettes. Retrieved from http://truthaboutecigs.
com/science/4.pdf
Kieckbush, R. (2010). Characterization of Regal cartridges for
electronic cigarettes. Retrieved from http://truthaboutecigs.com/
science/8.pdf
Laugesen, M. (2008). Safety report on the Ruyan e-cigarette
cartridge and inhaled aerosol (pp. 1–22), Christchurch, New
Zealand: Health New Zealand. Retrieved from http://www.
healthnz.co.nz/RuyanCartridgeReport30-Oct-08.pdf
Laugesen, M. (2010). Ruyan e-cigarette bench-top tests. Retrieved
from http://www.healthnz.co.nz/DublinEcigBenchtopHandout.pdf
National Institute for Occupational Safety and Health. (1998).
NIOSH Method 2551, Issue 1, Nicotine. NIOSH Manual Analytical
Methods (NMAM), Fourth Edition. Retrieved from http://www.
cdc.gov/niosh/docs/2003-154/pdfs/2551.pdf
Pauly, J., Li, Q., & Barry, M. B. (2007). Tobacco-free electronic
cigarettes and cigars deliver nicotine and generate concern.
Tobacco Control, 16, 357. doi:10.1136/tc.2006.019687
Trtchounian, A., & Talbot, P. (2010). Electronic nicotine delivery
systems: Is there a need for regulations? Tobacco Control, 20,
47–52. doi:10.1136/tc.2010.037259
Trtchounian, A., Williams, M., & Talbot, P. (2010). Conven-
tional and electronic cigarettes (e-cigarettes) have different
smoking characteristics. Nicotine & Tobacco Research, 12,
905–912. doi:10.1093/ntr/ntq114
Valance, C., & Ellicott, M. (2008). Analysis of chemical compo-
nents from High, Med &Low nicotine cartridges. Retrieved from
http://truthaboutecigs.com/science/12.pdf
Vansickel, A., Cobb, C., Weaver, M. F., & Eissenberg, T. E. (2010).
A clinical laboratory model for evaluating the acute effects of
electronic “cigarettes”: Nicotine delivery profile and cardiovascu-
lar and subjective effects. Cancer Epidemiology, Biomarkers &
Prevention, 19, 1945–1953. doi:10.1158/1055-9965.EPI-10-0288
Westenberger, B. J. (2009). Evaluation of e-cigarettes (pp. 1–8).
St. Louis, MO: Food and Drug Administration. Center for Drug
Evalation and Research. Retrieved from http://www.fda.gov/
downloads/Drugs/ScienceResearch/UCM173250.pdf
Williams, M., & Talbot, P. (2011). Variability among electronic
cigarettes in the pressure drop, airflow rate, and aerosol production.
Nicotine & Tobacco Research, 13, 1276–1283. doi:10.1093/ntr/ntr164
Wollscheid, K. A., & Kremzner, M. E. (2009). Electronic cigarettes:
Safety concerns and regulatory issues. American Journal of Health-
System Pharmacy, 66, 1740–1742. doi:10.2146/ajhp090127
at Society for Research on Nicotine and Tobacco member access on April 25, 2012http://ntr.oxfordjournals.org/Downloaded from
