What Is The Chemical Makeup Of Nicotine

Abstract

Introduction:

Electronic cigarette (e-cigarette) utilise is increasing dramatically in adult countries, simply little is known nigh these rapidly evolving products. This study analyzed and evaluated the chemical composition including nicotine, tobacco alkaloids, pH, and flavors in 36 e-liquids brands from 4 manufacturers.

Methods:

We determined the concentrations of nicotine, alkaloids, and select flavors and measured pH in solutions used in due east-cigarettes. E-cigarette products were chosen based upon favorable consumer approval ratings from online review websites. Quantitative analyses were performed using strict quality assurance/quality control validated methods previously established past our lab for the measurement of nicotine, alkaloids, pH, and flavors.

Results:

Three-quarters of the products contained lower measured nicotine levels than the stated characterization values (6%–42% by concentration). The pH for due east-liquids ranged from 5.1–9.1. Small-scale tobacco alkaloids were found in all samples containing nicotine, and their relative concentrations varied widely amongst manufacturers. A number of common flavor compounds were analyzed in all e-liquids.

Conclusions:

Free nicotine levels calculated from the measurement of pH correlated with total nicotine content. The direct correlation between the total nicotine concentration and pH suggests that the alkalinity of nicotine drives the pH of e-cigarette solutions. A higher per centum of nicotine exists in the more absorbable free grade every bit total nicotine concentration increases. A number of products contained tobacco alkaloids at concentrations that exceed U.S. pharmacopeia limits for impurities in nicotine used in pharmaceutical and food products.

Introduction

Electronic cigarettes (east-cigarettes) or electronic nicotine delivery systems (ENDS) are rapidly gaining acceptance amidst consumers and becoming a lucrative product in the tobacco marketplace. ^1,ii Recently, the Centers for Disease Control and Prevention reported that e-cigarette utilize doubled from January 2011 to January 2012 amidst teens. ³ East-cigarettes are battery powered droplets generating devices that utilize a resistive heating scroll to vaporize a solution containing propylene glycol, glycerin, flavors, frequently nicotine and sometimes ethanol and h2o. The solution, as well known equally e-liquid or e-juice, is independent in a dispensable or refillable cartridge depending on the design of the east-cigarette. Solutions for e-cigarettes are available in many flavors that almost often fall in 5 main categories: tobacco flavors (which are like to cigarettes), fruit flavors (blueberry, peach, etc.), menthol flavors, sweet flavors (candy, chocolate, etc.) and other flavors (java, black tea, wine, etc.). E-liquids are available in varying nicotine concentrations that typically range from 0mg/ml to 24mg/ml nicotine. ^4–vii

The typical e-cigarette oft resembles a traditional cigarette and consists of iii main parts: a bombardment, a cartridge, and an atomizer containing a heating coil, though more than contempo versions of e-cigarettes accept combined the cartridge and atomizer. When a user draws on an e-cigarette, a pressure level switch/sensor activates the heating element to vaporize the e-liquid, the vapor and so rapidly condenses to form an aerosol. A growing number of e-cigarette designs are currently on the market and these appear to be rapidly evolving to aid facilitate the delivery of nicotine to the consumer in a pleasing style. In add-on to the original e-cigarette design, numerous new, larger versions, ofttimes referred to equally tank systems are increasing in popularity. The tank e-cigarette devices are customizable and oft bear no resemblance to a cigarette. They besides ordinarily take a manually activated switch that turns on the heating coil. Because the e-cigarette'southward nicotine commitment is directly related to the ability delivery (wattage) of the device, tank e-cigarettes may incorporate a voltage tunable battery. ⁸ Users tin can so adjust or "tune" the voltage to evangelize their differing amounts of nicotine. E-cigarettes have become highly customizable to meet the specific needs of users. Customizable features include replaceable heating coils with 2 or more than wicks for improve vaporization and multiple chamber atomizers that claim to produce a more "robust" vapor. ^nine

Some manufacturers of e-cigarettes market the products as a safer alternative to combustible tobacco and in some cases imply that the products are gratuitous of harmful substances. While manufacturers practice not promote e-cigarettes as cessation devices, they take been investigated for this purpose with mixed results. Some literature has shown that e-cigarettes have shown some promise as a potential cessation tool for smoking. ¹⁰ For example, a recent report from the United Kingdom found that when e-cigarettes were used equally an assist for cessation, users were lx% more likely to sustain cessation when compared to conventional nicotine reduction therapies. ¹¹ Despite those results, a number of other studies have shown that eastward-cigarette use was non associated with smoking cessation. ^1,12,13 In addition, a recent study amid Korean adolescents showed that "adolescents who tried to quit smoking were more likely to apply e-cigarettes only less likely to no longer smoke, which suggests that e-cigarettes inhibit rather than promote abeyance." ^fourteen Similar results were observed for U.Southward. adolescents. ^fifteen Consumers may perceive that e-cigarettes are a condom alternative to cigarettes, which could increment experimentation. ¹⁶ However, the public health bear on of using east-cigarettes cannot be adequately assessed given the relatively limited and inconsistent data on east-cigarettes currently available.

In lodge to assess claims about the rubber of e-cigarettes, more research needs to be done to further examine the chemical contents of e-liquids. At that place are limited belittling data on chemicals in e-cigarette cartridges and refill solutions. Nicotine is the most widely studied constituent. Departure between labeled and measured concentrations of nicotine in refill solutions has been reported. ^17–26 The nicotine used in these devices is extracted from tobacco, and with it, other tobacco constituents are co-extracted. Other analytes of interest that have been tested in refill cartridges include tobacco-specific nitrosamines, ²⁷ aldehydes, ²⁸ tobacco alkaloids, ^{eighteen,23,25,26} and flavors. ²¹ The aim of this study was to provide further analysis of potentially harmful substances contained in due east-cigarettes. In order to help address the existing information gap, nosotros measured pH likewise equally the concentration of nicotine, tobacco alkaloids, and selected flavors constitute in the cartridges and refill solutions of 36 varieties of e-cigarettes using robust, quantitative, and validated methods.

Methods

Samples

East-cigarette materials were purchased online directly from 4 manufacturers (eSmoke, www.eSmoke.net; Premium, www.premiumecigarette.com; V2, world wide web.v2cigs.com; Due south Beach Smoke, www.southbeachsmoke.com). A full of 36 varieties (Due south Beach Fume, seven samples; V2, viii samples; Premium, 10 samples; eSmoke, 11 samples) were analyzed in this study. Brands were chosen based upon consumer approval ratings from online review websites (www.ecig-reviews.net, www.ecigcity.internet) at the time of buy. Upon receipt, samples were logged into a custom database, assigned barcodes with a unique bar-coded ID, and stored in their original containers until analyzed. Samples in cartridge form were uncapped and the solution soaked contents were removed. The saturated reservoir material was compressed inside a iii-ml disposable syringe and the liquid was nerveless in a vial. Liquid refill samples were used as provided past the manufacturers. For each product, only one manufacturer lot was analyzed; thus lot-to-lot variability was not assessed.

Reagents and Materials

Nicotine standards were purchased from AccuStandard. Quinoline used as an internal standard for nicotine was purchased from Sigma-Aldrich. Nicotiana glauca was purchased through Lab Depot. The pH calibration solutions were purchased from Command Visitor.

Alkaloid standards nornicotine, myosmine, anabasine, anatabine, and isonicoteine were purchased from Toronto Research Chemicals. Standards were purchased as racemic mixtures, if applicable. Isotopically labeled internal standard, (±) nornicotine-2,four,5,6-d₄ (pyridine-d₄), was purchased from CDN Isotopes; DL-Nicotine (methyl-d₃) was obtained from Cambridge Isotope Labs. These were added to samples and used for quantification.

Flavor standards (eucalyptol, camphor, menthol, methyl salicylate, pulegone, ethyl salicylate, cinnamaldehyde, eugenol, diphenyl ether, and coumarin) were purchased from Sigma-Aldrich. iii′,4′-(methylenedioxy)-acetophenone (MDA) was also purchased from Sigma-Aldrich and was used as an internal standard for quantifying flavour analytes. Research cigarettes, 3R4F, were obtained from the University of Kentucky and were used as matrix blank for spiking calibration standards. All other chemicals were of belittling form and were purchased through Fisher Scientific unless otherwise indicated.

Sample Preparation and Assay Procedures

Nicotine analysis was based on modifications to a previously reported method. ²⁹ Modifications include the apply of gas chromatography/tandem mass spectrometry (GC-MS/MS) (rather than GC-MS, gas chromatograpy-mass spectrometry) and a faster GC run time (2.3min vs. 3.7min). As well, the sample size was adjusted from 1,000mg to 400mg, and the corresponding standard and extraction solvent volumes were scaled appropriately.

The sample preparation for the nicotine method used a 400mg (±2mg) sample size. Samples of e-juice were weighed into a 15-ml amber vial, spiked with l µl of quinoline internal standard (10.5mg/ml), and 100 µl of alkaloids internal standard consisting of D_three-nicotine (0.38mg/ml) and D_iv-nornicotine (0.41mg/ml). A one-ml aliquot of 2N NaOH was added, and the sample was allowed to stand at room temperature for 15min. Afterwards, 10ml of methyl tert-butyl ether was added and the vials were capped and placed on a Rugged Rotator (Glass-Col) to tumble at 70 revolutions/min for 1hr. Later on agitation, sample extracts were expressed through a 0.45 µM filter straight into private GC vials. Samples were run in triplicate (N = 3) and analyzed. The GC-MS/MS hardware setup is the same for both the nicotine and alkaloids and because the internal standard for alkaloids was besides added, the same samples could be analyzed for minor tobacco alkaloids. The analysis of nicotine and minor alkaloids was performed using a split up injection and a separate method on the same instrument. Analysis was performed in triplicate (Northward = 3). Nicotine concentrations were reported in mg/g rather than mg/ml considering the verbal ratio of propylene glycol/glycerin in each due east-liquid was not known.

Triplicate (N = three) samples were prepared and analyzed for minor alkaloid concentrations using the methods previously outlined. ³⁰ Flavors analysis was also performed on triplicate samples (Due north = 3) using methods previously outlined by Lisko et al. ³¹ The pH analyses were washed using the method described in a Federal Register Notice, ³² and samples were analyzed in indistinguishable (North = 2).

Instrumentation and Apparatus

Flavors GC/MS analysis was performed using an Agilent 7890 GC coupled with a 5975 MSD (Agilent Technologies). The chromatographic separation was accomplished using an Ultra-ii capillary column (25 yard × 0.32mm × 0.52 µM) (Agilent Technologies) with research grade helium (>99.9999% purity) used as the carrier gas. Specific details of the previously validated method tin can exist found in Lisko et al. ³¹

Alkaloids GC-MS/MS analyses were performed using an Agilent 7890 GC coupled with a 7000 Triple-Quad detector. The chromatographic separation was accomplished using a DB-1701 capillary cavalcade (xxx m × 0.250 µM, 0.25 µM) (J&W Scientific) with research form (>99.9999% purity) helium used equally the carrier gas. Specific details of the previously validated method can be found in Lisko et al. ³⁰

Nicotine GC-MS/MS analysis was performed using an Agilent 7890 GC coupled with a 7000 Triple-Quad detector equipped with a CTC autosampler (Agilent Technologies), which injects ane µl of the extract per vial for assay. The split/splitless injector was maintained at 230 °C with a helium catamenia rate of one.7ml/min for 3min. Injections were made with a split ratio of 300:one with a solvent delay of ane.2min. The chromatographic separation (Supplementary Figure 1) was accomplished using a DB-1701 capillary cavalcade (30 m × 0.250 µM, 0.25 µM) (J&W Scientific) with research grade (>99.9999% purity) helium every bit the carrier gas. The GC ramp conditions were as follows: 175 °C for 0.1min; ramp at ten °C/min to 180 °C; and lastly ramp 75 °C/min to 240 °C. The total GC run time was 2.3min and the transfer line temperature was set to 285 °C. Compounds were ionized using electron impact ionization (70eV) in positive fashion and the ion source maintained at 280 °C. Mass measurements were made in Multiple Reaction Style. The retention times and 1000/z transition values chosen for detection are provided in Supplementary Table ane.

Standard curves were constructed by the analysis of N. glauca matrix spiked with known amounts of nicotine. North. glauca is an anabasine-rich tobacco species that contains no nicotine, which makes information technology an ideal matrix for scale. The scale range for the nicotine method was 0.05–42mg/thou and the limit of detection (LOD) was plant to exist 0.05mg/thou. The calculation of LOD was estimated as 3s₀, where southward₀ is the estimate of the standard departure at zero analyte concentration. The value of s₀ was taken as the y-intercept of a linear regression of standard departure versus concentration equally specified by Taylor et al. ³³ The method was validated by measuring the precision and accuracy of nicotine at three concentration levels. Precision/accuracy data were obtained by spiking v blank matrix samples at low, medium and high concentration levels of nicotine. A blank control was prepared by spiking v North. glauca matrix samples with internal standard only. The precision and accuracy of the method were plant to exist 3.1%–3.4% relative standard deviation (RSD) and 93.9%–97.9% recovery, respectively. A matrix comparison betwixt Northward. glauca and propylene glycol was too performed to ensure in that location were no matrix effects that should be considered when evaluating samples. Standard curves were injected in triplicate and the slopes and intercepts were compared. Slope differences less than 5% betoken an absence of matrix effects. A summary of the matrix comparison as well every bit the validation parameters can be establish in Supplementary Table two.

The pH analysis was performed on a Sirius Vinotrate (Sirius Analytical) according to the method outlined in the Federal Register. ³² We dissolved 500-mg samples in 5ml of distilled deionized water and determined an boilerplate pH measurement over a 1hr period. Constructed e-juice samples were prepared past dissolving a respective amount of commercially available nicotine (Sigma-Aldrich) in a 1:ane mixture of glycerin/propylene glycol to reflect concentrations of nicotine similar to those found in commercially available e-juice. Samples for pH analysis were run in duplicate (n = two). The percentage of nicotine in the freebase form was calculated using the Henderson-Hasselbach equation according to previously established methods. ³²

Results

Nicotine and Minor Tobacco Alkaloids

In agreement with previous literature reports, we institute the measured nicotine concentration was often significantly lower than the labeled nicotine concentrations in the refill solutions and e-liquid cartridges. Using the student t test, nosotros observed that the measured nicotine levels were statistically lower than the stated label values for all varieties from 3 of the 4 manufacturers (p < .03). Measured nicotine concentrations were five.8%–41.7% lower than the labeled nicotine values for Southward Beach Smoke, V2 and Premium manufacturers. Premium 6mg/ml eastward-liquid products were the to the lowest degree accurately labeled production tested, with 41.7% less nicotine in the liquid than specified on the product's labeling. Only 1 manufacturer, eSmoke, had nicotine levels on their labeling that was not statistically different than measured nicotine levels. Labeled nicotine concentrations for eSmoke products were within three.iv% of the measured nicotine concentration (Figure 1).

Figure i.

Measured nicotine concentrations were consistently lower than labeled amounts for all brands tested except eSmoke.

Figure 1.

Measured nicotine concentrations were consistently lower than labeled amounts for all brands tested except eSmoke.

Inconsistencies among the measured nicotine concentrations among different flavors with the same labeled nicotine concentration were most evident in V2 and Premium varieties. The V2 12mg Sahara and Peppermint flavors had measured nicotine concentrations of 11mg and nine.6mg, respectively. Similarly, Premium 24mg Tobacco and Peach flavors had measured concentrations that were quite different, 20.5mg and sixteen.5mg, respectively. While other researchers ²³ plant measureable levels of nicotine in e-liquids labeled equally containing no nicotine, nosotros did not observe measureable levels of nicotine in 0-mg refills and cartridges for the varieties tested from these 4 east-cigarette providers (LOD = 0.048mg/g).

Minor tobacco alkaloids, nornicotine, myosmine, anabasine, anatabine, and isonicoteine were found in all east-liquids tested that also contained nicotine (Table one). In traditional tobacco, there are direct correlations between nicotine and minor alkaloid concentrations. ³⁴ However, when examining the correlation of measured nicotine and modest alkaloids in east-liquids, the relationship was not equally consistent. Because of the structural similarity of the minor tobacco alkaloids and nicotine, extracts from tobacco to obtain nicotine used in east-liquids likely comprise differing concentrations of the minor alkaloids depending on purification or other manufacturing processes. This probable affects the relative concentrations of minor alkaloids with respect to nicotine.

Table 1.

Nicotine and Modest Tobacco Alkaloid Concentrations in 36 Electronic cigarette (E-Cigarette) Cartridges and Refill Solutions (Hateful ± SD) of Triplicate Measures of a Single Manufacturer Lot. U.S. Pharmacopeia (USP) Maximum Limits (0.five% for a Single Impurity [USP Single], 1.0% Total Impurities [USP Total]) for Impurities in Nicotine Take Been Calculated Based on the Measured Nicotine Concentrations

Flavour	Nicotine label concentration (mg)	NIC (mg/one thousand)	NNIC (µg/g)	MYOS (µg/g)	ANAB (µg/g)	ANAT (µg/g)	ISONIC (µg/g)	Total minor alkaloids (µg/g)	USP unmarried (µg/g)	USP total (µg/g)
South Beach Smoke
Vanilla	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Tobacco	half-dozen	4.5±0.one	5.six±0.two	v.8±0.2	3.8±0.two	6.6±0.two	1.31±0.01	23.0	22.v	45.0
Tobacco Blue	six	4.ii±0.2	6.4±0.1	8.8±0.iii	7.5±0.2	xi.2±0.ane	1.78±0.03	35.7	21.0	42.0
Tobacco Gold	12	9.seven±0.4	5.6±0.ane	xiii.iii±0.6	v.5±0.2	7.1±0.3	1.19±0.04	32.6	48.v	97.0
Peppermint	12	9.2±0.ii	four.8±0.2	11.2±0.4	8.5±0.two	nine.5±0.2	0.54±0.01	34.5	46.0	92.0
Menthol	16	thirteen.1±0.5	7.iii±0.2	11.7±0.3	9.6±0.4	15.0±0.vi	3.74±0.1	47.4	65.5	131.0
Peach	sixteen	12.2±0.ii	6.8±0.2	25.5±0.7	14.5±0.iv	22.5±0.3	0.72±0.02	seventy.0	61.0	122.0
V2
Menthol	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Peppermint	0	NT	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Sahara	6	5.4±0.2	1.85±0.03	2.9±0.ane	9.v±0.3	17.iv±0.4	0.84±0.02	32.four	27.0	54.0
Cherry	6	5.9±0.2	five.6±0.1	four.9±0.2	viii.2±0.2	19.i±0.3	0.70±0.02	38.4	29.5	59.0
Sahara	12	11.0±0.2	3.two±0.ane	5.two±0.ii	21.vi±0.7	41.6±0.vii	1.39±0.02	73.0	55.0	110.0
Peppermint	12	9.6±0.3	2.8±0.1	half dozen.0±0.3	20.0±0.5	33.five±0.six	1.17±0.01	63.5	48.0	96.0
Menthol	eighteen	15.3±0.4	two.3±0.1	ten.iv±0.2	14.6±0.5	23.0±0.2	four.42±0.1	54.vii	76.5	153.0
Red	18	16.7±0.6	18.7±0.2	26.1±0.8	62.8±iii.2	193.one±4.6	vii.97±0.3	308.6	83.v	167.0
Premium
Carmine	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Coffee	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Blueberry	half dozen	three.vii±0.2	v.ii±0.four	v.viii±0.3	6.vii±0.2	12.8±0.four	0.44±0.02	31.0	18.5	37.0
Watermelon	6	three.3±0.1	4.vii±0.i	v.0±0.two	6.ii±0.ane	11.2±0.3	0.37±0.01	27.4	sixteen.5	33.0
Pineapple	11	6.9±0.2	13.0±0.1	15.2±0.v	17.ix±0.5	62.1±2.ane	13.6±0.3	121.8	34.5	69.0
Menthol	xi	8.5±0.1	four.xvi±0.01	7.2±0.two	xvi.2±0.two	23.iii±0.iv	ane.24±0.02	52.1	42.5	85.0
Pear	16	10.1±0.iv	12.8±0.1	18.9±0.one	21.9±0.vii	40.1±0.9	1.49±0.02	95.1	l.5	101.0
Vanilla	16	thirteen.9±0.4	3.8±0.1	9.0±0.3	19.6±0.half-dozen	30.iii±0.4	1.42±0.02	64.two	69.5	139.0
Tobacco	24	20.5±0.9	viii.6±0.one	18.3±0.i	42.9±1.9	82.4±0.4	two.8±0.1	154.9	102.v	205.0
Peach	24	16.5±0.1	12.ix±0.2	17.3±0.iii	44.2±one.3	84.8±1.2	2.33±0.03	161.5	82.5	165.0
eSmoke
Morning Coffee	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Reddish El Toro	6	6.0±0.i	fifteen.2±1.0	17.3±0.7	37.7±ane.5	231.3±9.1	9.9±0.8	311.iv	30.0	60.0
Morn Coffee	six	half-dozen.1±0.1	six.three±0.2	9.seven±0.4	21.2±0.v	63.ane±1.eight	two.6±0.1	102.9	30.5	61.0
Dark-green Apple	half dozen	half-dozen.2±0.1	four.5±0.2	8.seven±0.2	21.7±0.6	68.8±2.9	2.38±0.03	106.0	31.0	62.0
Tobacco RY4	11	11.3±0.1	fourteen.4±0.four	xiv.v±0.7	40.6±0.5	130.9±four.8	5.6±0.ii	206.0	56.5	113.0
Minty Menthol	11	x.4±0.1	xi.five±0.two	62.7±2.i	seventy.6±2.0	361.1±13.six	20.7±0.5	526.7	52.0	104.0
Caribbean Kokosnoot	11	eleven.1±0.iii	8.0±0.ii	25.5±1.ane	53.0±2.7	171.six±6.4	four.4±0.2	262.v	55.5	111.0
Morn Coffee	eleven	eleven.2±0.2	11.3±0.2	xv.ane±0.four	42.four±0.half-dozen	131.7±3.three	half dozen.ane±0.one	206.vii	56.0	112.0
Morning Coffee	16	xvi.5±0.6	xix.7±0.two	28.vii±i.0	87.four±0.3	274.9±11.v	eight.8±0.1	419.iv	82.5	165.0
MTN Mist	16	xvi.half dozen±0.three	32.3±0.seven	35.half-dozen±0.nine	92.2±ane.7	300.iii±8.iii	7.1±0.i	467.six	83.0	166.0
Carmine El Toroa	24	NT	48.two±2.eight	41.5±0.7	152.2±iii.seven	485.4±five.vii	13.two±0.1	740.4	120.0	240.0

Flavor	Nicotine label concentration (mg)	NIC (mg/one thousand)	NNIC (µg/g)	MYOS (µg/g)	ANAB (µg/g)	ANAT (µg/one thousand)	ISONIC (µg/grand)	Total minor alkaloids (µg/g)	USP unmarried (µg/g)	USP total (µg/chiliad)
South Beach Smoke
Vanilla	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Tobacco	vi	four.5±0.1	v.6±0.2	v.8±0.two	3.8±0.2	6.half dozen±0.ii	1.31±0.01	23.0	22.five	45.0
Tobacco Blue	6	4.2±0.two	6.4±0.one	8.8±0.3	7.5±0.2	11.2±0.1	one.78±0.03	35.seven	21.0	42.0
Tobacco Gold	12	9.7±0.four	v.half-dozen±0.one	13.3±0.6	5.v±0.2	7.1±0.3	1.19±0.04	32.6	48.5	97.0
Peppermint	12	9.2±0.ii	iv.viii±0.2	11.ii±0.4	eight.five±0.2	9.v±0.2	0.54±0.01	34.v	46.0	92.0
Menthol	16	13.1±0.v	seven.3±0.2	11.7±0.3	9.6±0.iv	fifteen.0±0.6	three.74±0.1	47.4	65.five	131.0
Peach	16	12.2±0.2	half dozen.8±0.2	25.5±0.7	14.v±0.4	22.five±0.3	0.72±0.02	lxx.0	61.0	122.0
V2
Menthol	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Peppermint	0	NT	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Sahara	vi	5.4±0.ii	1.85±0.03	two.9±0.1	nine.5±0.3	17.4±0.4	0.84±0.02	32.4	27.0	54.0
Red	half dozen	v.9±0.2	5.6±0.ane	4.nine±0.ii	eight.2±0.2	xix.i±0.3	0.70±0.02	38.4	29.5	59.0
Sahara	12	11.0±0.2	three.2±0.one	5.2±0.ii	21.6±0.seven	41.6±0.seven	ane.39±0.02	73.0	55.0	110.0
Peppermint	12	9.6±0.three	2.8±0.1	6.0±0.3	20.0±0.five	33.v±0.6	one.17±0.01	63.5	48.0	96.0
Menthol	18	15.3±0.four	2.3±0.1	10.four±0.two	fourteen.vi±0.v	23.0±0.2	4.42±0.i	54.7	76.5	153.0
Cherry-red	18	sixteen.seven±0.half-dozen	18.vii±0.2	26.one±0.8	62.8±three.ii	193.ane±4.6	vii.97±0.3	308.six	83.five	167.0
Premium
Ruby	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Java	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Blueberry	six	3.7±0.2	5.2±0.4	5.viii±0.3	six.7±0.2	12.8±0.4	0.44±0.02	31.0	18.5	37.0
Watermelon	6	three.3±0.1	iv.vii±0.i	5.0±0.2	6.two±0.1	11.two±0.iii	0.37±0.01	27.4	16.5	33.0
Pineapple	11	half-dozen.9±0.two	xiii.0±0.i	15.two±0.5	17.9±0.5	62.1±ii.1	xiii.six±0.3	121.eight	34.5	69.0
Menthol	11	8.five±0.1	4.xvi±0.01	seven.two±0.2	16.two±0.two	23.3±0.four	one.24±0.02	52.i	42.5	85.0
Pear	16	10.1±0.four	12.viii±0.1	18.9±0.i	21.nine±0.7	40.ane±0.ix	i.49±0.02	95.i	50.5	101.0
Vanilla	16	13.9±0.iv	3.eight±0.ane	9.0±0.3	19.half-dozen±0.6	30.3±0.4	one.42±0.02	64.ii	69.5	139.0
Tobacco	24	20.5±0.9	8.vi±0.1	18.3±0.ane	42.ix±ane.9	82.4±0.4	2.8±0.one	154.nine	102.5	205.0
Peach	24	16.five±0.1	12.9±0.2	17.3±0.iii	44.2±i.3	84.viii±1.ii	ii.33±0.03	161.5	82.5	165.0
eSmoke
Morning Coffee	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Red El Toro	half-dozen	half-dozen.0±0.1	fifteen.2±1.0	17.3±0.seven	37.7±1.five	231.iii±9.one	nine.nine±0.8	311.four	30.0	60.0
Morning time Java	six	6.i±0.1	vi.3±0.2	9.seven±0.four	21.2±0.5	63.ane±1.8	2.half dozen±0.1	102.9	30.5	61.0
Green Apple	6	vi.2±0.i	4.5±0.2	8.seven±0.2	21.vii±0.6	68.8±ii.ix	2.38±0.03	106.0	31.0	62.0
Tobacco RY4	11	11.3±0.one	14.4±0.four	fourteen.5±0.7	twoscore.6±0.5	130.9±4.viii	5.6±0.2	206.0	56.5	113.0
Minty Menthol	eleven	10.4±0.1	11.5±0.ii	62.7±2.1	seventy.six±two.0	361.1±13.vi	twenty.7±0.5	526.7	52.0	104.0
Caribbean area Coconut	eleven	11.ane±0.iii	8.0±0.ii	25.5±1.1	53.0±2.7	171.six±six.4	4.four±0.two	262.5	55.5	111.0
Morning time Coffee	11	11.two±0.two	11.iii±0.2	15.1±0.4	42.4±0.6	131.seven±3.3	vi.1±0.one	206.7	56.0	112.0
Morning Java	16	16.5±0.6	19.seven±0.2	28.7±i.0	87.4±0.three	274.9±11.five	eight.viii±0.1	419.4	82.5	165.0
MTN Mist	16	16.6±0.3	32.3±0.7	35.6±0.ix	92.two±1.7	300.3±8.3	seven.1±0.ane	467.6	83.0	166.0
Cerise El Toroa	24	NT	48.2±two.viii	41.5±0.7	152.2±3.7	485.4±five.7	13.2±0.i	740.4	120.0	240.0

ANAB = Anabasine; ANAT = Anatabine; ISONIC = Isonicoteine; LOD = limit of detection; MYOS = Myosmine; NA = not applicable; NIC = nicotine; NNIC = nornicotine; NT = non tested.

^aUSP calculated values are based on the labeled nicotine concentration since the sample was not available for nicotine testing.

Table ane.

Nicotine and Pocket-sized Tobacco Alkaloid Concentrations in 36 Electronic cigarette (E-Cigarette) Cartridges and Refill Solutions (Hateful ± SD) of Triplicate Measures of a Unmarried Manufacturer Lot. U.S. Pharmacopeia (USP) Maximum Limits (0.five% for a Single Impurity [USP Unmarried], 1.0% Total Impurities [USP Full]) for Impurities in Nicotine Have Been Calculated Based on the Measured Nicotine Concentrations

Flavour	Nicotine label concentration (mg)	NIC (mg/thousand)	NNIC (µg/g)	MYOS (µg/g)	ANAB (µg/chiliad)	ANAT (µg/g)	ISONIC (µg/g)	Total minor alkaloids (µg/thousand)	USP single (µg/g)	USP full (µg/g)
South Beach Fume
Vanilla	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Tobacco	half-dozen	4.five±0.1	v.six±0.2	5.8±0.2	iii.8±0.2	6.6±0.2	ane.31±0.01	23.0	22.5	45.0
Tobacco Blue	6	4.2±0.2	half dozen.4±0.ane	8.8±0.iii	7.5±0.ii	xi.ii±0.ane	1.78±0.03	35.7	21.0	42.0
Tobacco Golden	12	9.7±0.iv	5.half dozen±0.1	13.3±0.6	5.5±0.two	7.1±0.3	1.19±0.04	32.six	48.v	97.0
Peppermint	12	ix.2±0.2	4.eight±0.2	11.ii±0.4	8.v±0.2	nine.five±0.2	0.54±0.01	34.v	46.0	92.0
Menthol	16	13.1±0.5	seven.iii±0.ii	eleven.seven±0.three	ix.6±0.4	15.0±0.6	three.74±0.1	47.4	65.5	131.0
Peach	16	12.2±0.ii	6.8±0.2	25.v±0.7	14.v±0.iv	22.v±0.three	0.72±0.02	seventy.0	61.0	122.0
V2
Menthol	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Peppermint	0	NT	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Sahara	half dozen	5.4±0.2	1.85±0.03	2.ix±0.1	ix.v±0.3	17.four±0.4	0.84±0.02	32.4	27.0	54.0
Red	6	5.9±0.2	5.six±0.1	four.ix±0.two	8.2±0.2	19.ane±0.3	0.70±0.02	38.4	29.5	59.0
Sahara	12	11.0±0.ii	3.two±0.i	5.2±0.ii	21.6±0.7	41.half-dozen±0.7	1.39±0.02	73.0	55.0	110.0
Peppermint	12	nine.half dozen±0.3	2.eight±0.1	half-dozen.0±0.3	twenty.0±0.v	33.five±0.six	i.17±0.01	63.5	48.0	96.0
Menthol	18	xv.3±0.4	2.iii±0.1	10.4±0.2	14.half-dozen±0.five	23.0±0.2	4.42±0.1	54.vii	76.5	153.0
Red	18	16.vii±0.half-dozen	eighteen.seven±0.2	26.one±0.eight	62.8±3.ii	193.one±four.6	7.97±0.3	308.half-dozen	83.v	167.0
Premium
Red	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Coffee	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Blueberry	6	three.7±0.2	5.2±0.4	five.8±0.3	six.7±0.2	12.8±0.4	0.44±0.02	31.0	eighteen.v	37.0
Watermelon	6	3.3±0.1	4.vii±0.1	5.0±0.2	half-dozen.2±0.1	11.two±0.3	0.37±0.01	27.4	16.5	33.0
Pineapple	xi	half-dozen.9±0.2	thirteen.0±0.1	15.2±0.5	17.9±0.5	62.1±ii.i	13.6±0.three	121.eight	34.5	69.0
Menthol	eleven	8.5±0.1	4.xvi±0.01	7.ii±0.2	xvi.ii±0.2	23.iii±0.4	i.24±0.02	52.1	42.5	85.0
Pear	16	10.ane±0.4	12.viii±0.one	18.9±0.one	21.9±0.7	40.i±0.9	1.49±0.02	95.i	50.5	101.0
Vanilla	sixteen	13.9±0.iv	3.8±0.1	ix.0±0.3	19.6±0.6	30.3±0.iv	1.42±0.02	64.2	69.five	139.0
Tobacco	24	20.v±0.9	8.6±0.ane	18.3±0.one	42.9±1.9	82.four±0.4	two.eight±0.1	154.9	102.5	205.0
Peach	24	xvi.v±0.1	12.ix±0.ii	17.iii±0.3	44.two±1.iii	84.8±1.two	2.33±0.03	161.5	82.5	165.0
eSmoke
Morn Coffee	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Cherry El Toro	half dozen	six.0±0.1	fifteen.2±one.0	17.iii±0.7	37.seven±1.5	231.three±9.1	9.9±0.viii	311.4	xxx.0	60.0
Morn Coffee	six	half-dozen.ane±0.1	6.3±0.2	9.7±0.four	21.2±0.5	63.1±i.8	two.half dozen±0.1	102.ix	30.5	61.0
Light-green Apple tree	6	vi.2±0.1	iv.v±0.ii	8.7±0.2	21.7±0.vi	68.viii±2.ix	2.38±0.03	106.0	31.0	62.0
Tobacco RY4	11	11.iii±0.1	14.4±0.iv	fourteen.5±0.7	40.half-dozen±0.5	130.9±4.eight	v.6±0.2	206.0	56.v	113.0
Minty Menthol	11	10.four±0.1	eleven.v±0.2	62.7±2.one	70.half dozen±2.0	361.1±xiii.half-dozen	20.seven±0.five	526.7	52.0	104.0
Caribbean area Coconut	xi	eleven.ane±0.3	8.0±0.2	25.five±1.1	53.0±2.seven	171.6±half-dozen.4	4.4±0.2	262.five	55.5	111.0
Morning Coffee	xi	11.2±0.2	11.three±0.two	15.ane±0.4	42.4±0.six	131.7±3.3	6.1±0.ane	206.7	56.0	112.0
Morning Java	16	16.5±0.6	nineteen.7±0.2	28.seven±one.0	87.four±0.iii	274.9±11.5	eight.8±0.ane	419.iv	82.v	165.0
MTN Mist	16	16.half-dozen±0.3	32.3±0.7	35.6±0.nine	92.2±one.7	300.iii±8.3	7.1±0.1	467.6	83.0	166.0
Red El Toroa	24	NT	48.2±two.eight	41.5±0.seven	152.2±three.7	485.4±v.seven	13.2±0.ane	740.four	120.0	240.0

Flavor	Nicotine label concentration (mg)	NIC (mg/g)	NNIC (µg/chiliad)	MYOS (µg/g)	ANAB (µg/g)	ANAT (µg/grand)	ISONIC (µg/thousand)	Total minor alkaloids (µg/g)	USP single (µg/g)	USP total (µg/k)
South Beach Fume
Vanilla	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Tobacco	vi	4.5±0.i	v.vi±0.two	5.viii±0.2	3.8±0.ii	6.6±0.ii	1.31±0.01	23.0	22.5	45.0
Tobacco Blueish	half-dozen	four.two±0.two	6.4±0.1	8.8±0.3	7.5±0.ii	11.2±0.1	1.78±0.03	35.7	21.0	42.0
Tobacco Gilt	12	9.seven±0.iv	v.6±0.1	xiii.iii±0.6	5.5±0.2	7.1±0.iii	1.nineteen±0.04	32.half-dozen	48.5	97.0
Peppermint	12	9.2±0.2	4.8±0.2	11.two±0.4	8.five±0.2	9.v±0.2	0.54±0.01	34.5	46.0	92.0
Menthol	sixteen	xiii.one±0.5	7.3±0.ii	11.vii±0.three	nine.6±0.four	15.0±0.6	3.74±0.ane	47.4	65.v	131.0
Peach	16	12.2±0.ii	six.8±0.ii	25.v±0.seven	14.5±0.4	22.5±0.3	0.72±0.02	70.0	61.0	122.0
V2
Menthol	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Peppermint	0	NT	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Sahara	6	v.iv±0.2	1.85±0.03	ii.nine±0.ane	9.v±0.iii	17.iv±0.4	0.84±0.02	32.4	27.0	54.0
Carmine	half-dozen	v.9±0.2	5.6±0.ane	4.nine±0.2	viii.2±0.2	19.one±0.three	0.70±0.02	38.4	29.5	59.0
Sahara	12	11.0±0.two	3.two±0.ane	5.2±0.2	21.6±0.7	41.6±0.7	one.39±0.02	73.0	55.0	110.0
Peppermint	12	nine.half-dozen±0.3	2.8±0.i	6.0±0.three	20.0±0.v	33.5±0.6	1.17±0.01	63.5	48.0	96.0
Menthol	18	15.3±0.4	two.3±0.1	10.four±0.2	14.6±0.5	23.0±0.ii	4.42±0.one	54.seven	76.5	153.0
Red	18	16.vii±0.half dozen	18.7±0.2	26.1±0.8	62.8±3.2	193.1±4.half-dozen	7.97±0.iii	308.vi	83.v	167.0
Premium
Carmine	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Coffee	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Blueberry	vi	three.vii±0.two	5.2±0.4	five.8±0.3	6.7±0.2	12.eight±0.4	0.44±0.02	31.0	18.v	37.0
Watermelon	half dozen	three.3±0.1	four.vii±0.one	5.0±0.two	6.2±0.1	xi.2±0.iii	0.37±0.01	27.4	16.5	33.0
Pineapple	11	6.9±0.2	13.0±0.1	xv.ii±0.5	17.nine±0.5	62.1±2.1	13.6±0.3	121.8	34.5	69.0
Menthol	eleven	8.five±0.1	iv.sixteen±0.01	7.two±0.two	xvi.2±0.2	23.3±0.iv	1.24±0.02	52.ane	42.5	85.0
Pear	16	x.ane±0.4	12.viii±0.ane	18.ix±0.1	21.9±0.seven	twoscore.ane±0.9	i.49±0.02	95.1	50.5	101.0
Vanilla	16	13.ix±0.four	iii.8±0.1	ix.0±0.3	19.half-dozen±0.vi	30.3±0.four	1.42±0.02	64.2	69.5	139.0
Tobacco	24	20.5±0.9	8.6±0.one	eighteen.3±0.1	42.ix±ane.ix	82.4±0.4	ii.8±0.1	154.9	102.five	205.0
Peach	24	16.5±0.1	12.9±0.2	17.3±0.iii	44.2±i.3	84.8±ane.2	2.33±0.03	161.five	82.5	165.0
eSmoke
Morn Coffee	0	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD	NA	NA
Red El Toro	vi	6.0±0.1	fifteen.two±one.0	17.iii±0.7	37.7±1.5	231.3±9.1	9.nine±0.eight	311.4	xxx.0	60.0
Morn Coffee	6	6.1±0.ane	6.3±0.two	ix.7±0.4	21.2±0.5	63.1±i.8	2.six±0.1	102.9	30.5	61.0
Green Apple	6	6.two±0.one	4.5±0.2	8.7±0.2	21.7±0.6	68.8±two.9	ii.38±0.03	106.0	31.0	62.0
Tobacco RY4	11	11.iii±0.1	14.4±0.iv	14.5±0.seven	40.6±0.5	130.9±4.8	five.vi±0.ii	206.0	56.5	113.0
Minty Menthol	11	10.4±0.1	11.5±0.2	62.7±2.1	70.6±2.0	361.1±13.6	twenty.vii±0.5	526.7	52.0	104.0
Caribbean Coconut	xi	11.1±0.3	viii.0±0.ii	25.five±1.1	53.0±2.7	171.6±6.4	4.4±0.two	262.5	55.5	111.0
Morning Coffee	11	11.two±0.two	11.three±0.2	15.1±0.four	42.4±0.6	131.7±iii.iii	6.1±0.one	206.7	56.0	112.0
Forenoon Coffee	16	16.5±0.6	19.seven±0.ii	28.7±i.0	87.4±0.three	274.nine±xi.v	8.8±0.1	419.4	82.5	165.0
MTN Mist	16	16.6±0.three	32.3±0.seven	35.6±0.9	92.2±one.7	300.three±viii.3	7.1±0.1	467.6	83.0	166.0
Red El Toroa	24	NT	48.two±2.eight	41.five±0.7	152.2±3.7	485.iv±5.7	13.2±0.one	740.4	120.0	240.0

ANAB = Anabasine; ANAT = Anatabine; ISONIC = Isonicoteine; LOD = limit of detection; MYOS = Myosmine; NA = not applicable; NIC = nicotine; NNIC = nornicotine; NT = non tested.

^aUSP calculated values are based on the labeled nicotine concentration since the sample was not available for nicotine testing.

Poor quality control is some other explanation for the poor correlation between nicotine and pocket-size alkaloids. Among the samples tested, a number of samples with similar measured nicotine concentrations had widely varying pocket-size alkaloid concentrations. For example, V2 18mg Menthol season and V2 18mg Red flavor had anatabine levels of 23 and 193 µg/g, respectively. As well, eSmoke 11mg Minty Menthol flavor and 11mg Forenoon Coffee flavour had myosmine levels of 62.7 and xv.1 µg/g, respectively. Potentially, these flavors may have been made with different lots of nicotine solution but without knowing the manufacturing process, it is incommunicable to determine the cause of the variation.

The American e-Liquid Manufacturing Standards Clan, an manufacture group with no regulatory authority, calls for the utilise of U.Southward. pharmacopeia (USP) class nicotine in their e-liquid products. ³⁵ USP specifications of nicotine purity allow for a maximum of 0.v% (5mg/g) of a single impurity and 1.0% (10mg/g) total impurities. ³⁶ For example, a product containing 15.0mg/m of nicotine tin can have up to 75 µg/m of a single impurity and a maximum of 150 µg/grand full impurities. For the products tested, the majority of products tested had impurities that did not exceed USP limits, however, total alkaloid concentrations institute in eSmoke brand exceeded USP limits in all products (Tabular array 1). The V2 Reddish 18mg solution likewise equally Premium Pineapple 11mg and Premium Peach 24mg solutions each had a single impurity (anatabine) that exceeded USP limits. Total alkaloids for the V2 Red 18-mg solution and the Premium Pineapple 11-mg solutions also exceed the proposed USP limits.

It is important to note, all the same, that when nicotine is exposed to air, oxidation can occur which results in the generation of small-scale alkaloids. ^37,38 Because the rate of oxidation in eastward-liquids has not been reported and the time between due east-liquid production and testing is non known, it is difficult to assess the concentrations of alkaloids due to nicotine oxidation. Regardless of the source of alkaloids, whether the nicotine was exposed to air during manufacturing or an impure nicotine source was used, a number of samples were found to have alkaloid impurities that exceed USP specifications. While the health implications of select impurities are non known, we draw attention here to illustrate differences in the manufacturers approach to production design.

The small-scale tobacco alkaloid concentrations in e-liquids are generally much lower when compared to traditional cigarettes. Traditional cigarettes have minor tobacco alkaloid concentrations in the range of 659–986 µg/thousand for nornicotine, 8.6–17.3 µg/g for myosmine, 127–185 µg/g for anabasine, 927–ane,390 µg/1000 for anatabine and 23.iv–45.5 µg/g for isonicoteine. ^xxx eSmoke e-liquids had the highest concentrations of the minor tobacco alkaloids (6.3–48.ii µg/g nornicotine, 8.seven–62.seven µg/g myosmine, 21.2–152 µg/g anabasine, 63.ane–485 µg/g anatabine, and 2.four–twenty.7 µg/g isonicoteine). South Beach Smoke, V2 and Premium products contained considerably less alkaloid content, suggesting a either a more pure nicotine extract was used or nicotine oxidation was minimized for those refill cartridges.

Flavors

We tested the 36 e-cigarette products for ten flavour compounds commonly used equally additives in tobacco products. These compounds included eucalyptol, camphor, menthol, methyl salicylate, pulegone, ethyl salicylate, cinnamaldehyde, eugenol, diphenyl ether, and coumarin (Tabular array ii). Measureable levels of eucalyptol (<LOD—87 µg/g) and pulegone (<LOD—115 µg/g) were found in the menthol flavored varieties for all manufacturers. Menthol concentrations ranged from 3,700 to 12,000 µg/thou in flavored e-liquids, which is like to levels plant in commercial cigarette filler. ^39,40 Menthol and pulegone are typical flavors found in mint products besides. Interestingly, menthol was also constitute at low concentrations in forty% of the tobacco-flavored non-menthol products tested in this study. Tobacco Gold flavour (Due south Embankment Fume) as well every bit Sahara and Scarlet flavors (V2) contained low concentrations of menthol (half-dozen.ii–14.7 µg/g). Added menthol may reduce harshness or more closely simulate the sensory experience of smoking traditional cigarettes.

Tabular array 2.

Concentrations (µg/g, Northward = 3) of Selected Flavor Analytes^a in Electronic cigarette (E-Cigarette) Cartridges or Refill Solutions

Flavor	Nicotine label concentration (mg)	EUC	CAM	MEN	PUL	CINN	ESAL
S Beach Smoke
Vanilla	0	–	–	–	–	–	–
Tobacco	half dozen	–	–	–	–	–	–
Tobacco Blue	vi	–	–	–	–	–	–
Tobacco Gold	12	–	10.two±2.one	half dozen.2±0.8	–	–	–
Peppermint	12	–	–	iii,670±161	25.vii±i.0	47.1±0.ix	–
Peach	sixteen	–	–	–	–	–	–
Menthol	16	24.five±0.4	–	7,780±141	28.2±0.4	–	–
V2
Menthol	0	21.vi±0.five	–	11,200±428	119±3.8	–	–
Menthol	xviii	39.4±0.8	–	eleven,100±246	l.1±0.9	–	–
Sahara	six	–	–	xiv.7±5.four	–	–	–
Sahara	12	–	–	13.1±1.8	–	–	–
Red	6	–	–	–	–	–	–
Ruby-red	18	–	–	13.six±one.0	–	–	–
Peppermint	0	–	5.9±0.4	nine,770±307	78.iii±1.7	37.6±0.ii	–
Peppermint	12	–	five.8±0.v	ix,530±281	82.7±1.9	10.4±0.4	–
Premium
Cherry	0	–	one,310±75.3	–	–	–	13.0±0.6
Coffee	0	–	–	–	–	–	–
Watermelon	6	–	–	–	–	–	–
Huckleberry	half dozen	–	278±8.9	–	–	–	–
Pineapple	11	–	13.three±2.0	–	–	–	–
Menthol	11	86.viii±3.iv	–	12,400±468	115±2.viii	98.6±2.2	–
Pear	xvi	–	–	–	–	–	–
Vanilla	16	–	–	–	–	–	–
Tobacco	24	–	–	–	–	–	–
Peach	24	–	–	–	–	–	–
eSmoke
Forenoon Coffee	0	–	–	–	–	–	–
Morning Coffee	vi	–	–	–	–	–	–
Morning Coffee	11	–	–	–	–	–	–
Morning Coffee	sixteen	–	–	–	–	–	–
Red El Toro	6	–	–	–	–	–	–
Green Apple tree	6	–	–	–	–	–	–
Tobacco	11	–	–	–	–	–	–
Minty Menthol	eleven	twenty.iii±0.7	–	four,860±150	10.five±0.6	–	–
Caribbean Kokosnoot	11	–	–	–	–	–	–
MTN Mist	xvi	–	nine.9±ane.6	–	–	–	–
Red El Toro	24	–	–	–	–	–	–

Flavor	Nicotine label concentration (mg)	EUC	CAM	MEN	PUL	CINN	ESAL
S Beach Smoke
Vanilla	0	–	–	–	–	–	–
Tobacco	6	–	–	–	–	–	–
Tobacco Bluish	6	–	–	–	–	–	–
Tobacco Gold	12	–	10.ii±ii.ane	vi.2±0.eight	–	–	–
Peppermint	12	–	–	iii,670±161	25.seven±1.0	47.ane±0.ix	–
Peach	16	–	–	–	–	–	–
Menthol	16	24.five±0.four	–	7,780±141	28.ii±0.4	–	–
V2
Menthol	0	21.half-dozen±0.5	–	11,200±428	119±3.8	–	–
Menthol	eighteen	39.four±0.8	–	xi,100±246	fifty.1±0.ix	–	–
Sahara	half-dozen	–	–	fourteen.7±5.4	–	–	–
Sahara	12	–	–	13.one±i.8	–	–	–
Red	six	–	–	–	–	–	–
Red	eighteen	–	–	thirteen.vi±1.0	–	–	–
Peppermint	0	–	5.nine±0.4	9,770±307	78.iii±ane.7	37.vi±0.ii	–
Peppermint	12	–	5.eight±0.5	9,530±281	82.7±1.9	x.4±0.4	–
Premium
Cerise	0	–	1,310±75.3	–	–	–	thirteen.0±0.6
Coffee	0	–	–	–	–	–	–
Watermelon	6	–	–	–	–	–	–
Blueberry	6	–	278±8.ix	–	–	–	–
Pineapple	11	–	13.3±two.0	–	–	–	–
Menthol	11	86.eight±3.4	–	12,400±468	115±2.eight	98.half-dozen±2.2	–
Pear	16	–	–	–	–	–	–
Vanilla	16	–	–	–	–	–	–
Tobacco	24	–	–	–	–	–	–
Peach	24	–	–	–	–	–	–
eSmoke
Morn Coffee	0	–	–	–	–	–	–
Morning Coffee	6	–	–	–	–	–	–
Morning Coffee	xi	–	–	–	–	–	–
Morning Java	16	–	–	–	–	–	–
Carmine El Toro	half-dozen	–	–	–	–	–	–
Greenish Apple	vi	–	–	–	–	–	–
Tobacco	11	–	–	–	–	–	–
Minty Menthol	11	twenty.3±0.7	–	4,860±150	x.v±0.6	–	–
Caribbean Coconut	11	–	–	–	–	–	–
MTN Mist	16	–	9.9±one.six	–	–	–	–
Crimson El Toro	24	–	–	–	–	–	–

– = <LOD; CAM = camphor; CINN = cinnamaldehyde; ESAL = ethyl salicylate; EUC = eucalyptol; LOD = limit of detection; MEN = menthol, PUL = pulegone.

^aAll e-cigarette samples were also tested for diphenyl ether, coumarin, methyl salicylate, and eugenol merely these flavour analytes were not detected.

Table two.

Concentrations (µg/chiliad, N = 3) of Selected Flavor Analytes^a in Electronic cigarette (E-Cigarette) Cartridges or Refill Solutions

Flavor	Nicotine label concentration (mg)	EUC	CAM	MEN	PUL	CINN	ESAL
South Beach Smoke
Vanilla	0	–	–	–	–	–	–
Tobacco	6	–	–	–	–	–	–
Tobacco Blue	6	–	–	–	–	–	–
Tobacco Gilt	12	–	10.two±2.1	vi.2±0.eight	–	–	–
Peppermint	12	–	–	3,670±161	25.7±one.0	47.one±0.nine	–
Peach	16	–	–	–	–	–	–
Menthol	16	24.5±0.4	–	7,780±141	28.ii±0.iv	–	–
V2
Menthol	0	21.6±0.5	–	eleven,200±428	119±3.8	–	–
Menthol	18	39.four±0.8	–	11,100±246	50.ane±0.9	–	–
Sahara	6	–	–	14.7±5.four	–	–	–
Sahara	12	–	–	thirteen.one±ane.8	–	–	–
Red	6	–	–	–	–	–	–
Blood-red	18	–	–	xiii.6±1.0	–	–	–
Peppermint	0	–	5.ix±0.4	9,770±307	78.three±i.7	37.6±0.2	–
Peppermint	12	–	5.8±0.5	ix,530±281	82.vii±1.ix	ten.4±0.4	–
Premium
Blood-red	0	–	1,310±75.3	–	–	–	thirteen.0±0.6
Coffee	0	–	–	–	–	–	–
Watermelon	six	–	–	–	–	–	–
Huckleberry	6	–	278±viii.nine	–	–	–	–
Pineapple	xi	–	thirteen.3±2.0	–	–	–	–
Menthol	11	86.eight±iii.4	–	12,400±468	115±ii.viii	98.vi±2.2	–
Pear	sixteen	–	–	–	–	–	–
Vanilla	sixteen	–	–	–	–	–	–
Tobacco	24	–	–	–	–	–	–
Peach	24	–	–	–	–	–	–
eSmoke
Morning Java	0	–	–	–	–	–	–
Morning Coffee	6	–	–	–	–	–	–
Morning Coffee	11	–	–	–	–	–	–
Morn Coffee	16	–	–	–	–	–	–
Red El Toro	6	–	–	–	–	–	–
Green Apple	6	–	–	–	–	–	–
Tobacco	11	–	–	–	–	–	–
Minty Menthol	xi	20.3±0.seven	–	4,860±150	x.v±0.six	–	–
Caribbean Coconut	11	–	–	–	–	–	–
MTN Mist	16	–	9.nine±1.6	–	–	–	–
Red El Toro	24	–	–	–	–	–	–

Season	Nicotine label concentration (mg)	EUC	CAM	MEN	PUL	CINN	ESAL
Due south Beach Smoke
Vanilla	0	–	–	–	–	–	–
Tobacco	vi	–	–	–	–	–	–
Tobacco Blue	6	–	–	–	–	–	–
Tobacco Gold	12	–	10.2±ii.ane	6.2±0.8	–	–	–
Peppermint	12	–	–	3,670±161	25.vii±ane.0	47.1±0.9	–
Peach	16	–	–	–	–	–	–
Menthol	16	24.v±0.4	–	7,780±141	28.2±0.4	–	–
V2
Menthol	0	21.half-dozen±0.5	–	xi,200±428	119±iii.8	–	–
Menthol	eighteen	39.iv±0.eight	–	11,100±246	50.1±0.9	–	–
Sahara	half-dozen	–	–	14.seven±v.4	–	–	–
Sahara	12	–	–	13.1±1.eight	–	–	–
Cherry-red	6	–	–	–	–	–	–
Crimson	xviii	–	–	13.6±one.0	–	–	–
Peppermint	0	–	v.ix±0.4	9,770±307	78.three±1.7	37.6±0.2	–
Peppermint	12	–	5.8±0.5	9,530±281	82.seven±ane.9	x.4±0.4	–
Premium
Carmine	0	–	1,310±75.3	–	–	–	13.0±0.half dozen
Java	0	–	–	–	–	–	–
Watermelon	6	–	–	–	–	–	–
Blueberry	6	–	278±8.9	–	–	–	–
Pineapple	xi	–	13.3±2.0	–	–	–	–
Menthol	xi	86.8±3.4	–	12,400±468	115±2.eight	98.6±2.two	–
Pear	sixteen	–	–	–	–	–	–
Vanilla	xvi	–	–	–	–	–	–
Tobacco	24	–	–	–	–	–	–
Peach	24	–	–	–	–	–	–
eSmoke
Morning Coffee	0	–	–	–	–	–	–
Morning Coffee	half dozen	–	–	–	–	–	–
Morning Coffee	11	–	–	–	–	–	–
Forenoon Coffee	xvi	–	–	–	–	–	–
Cerise El Toro	half dozen	–	–	–	–	–	–
Dark-green Apple	six	–	–	–	–	–	–
Tobacco	xi	–	–	–	–	–	–
Minty Menthol	xi	xx.iii±0.7	–	iv,860±150	10.v±0.6	–	–
Caribbean area Kokosnoot	eleven	–	–	–	–	–	–
MTN Mist	16	–	9.9±1.6	–	–	–	–
Carmine El Toro	24	–	–	–	–	–	–

– = <LOD; CAM = camphor; CINN = cinnamaldehyde; ESAL = ethyl salicylate; EUC = eucalyptol; LOD = limit of detection; MEN = menthol, PUL = pulegone.

^aAll e-cigarette samples were also tested for diphenyl ether, coumarin, methyl salicylate, and eugenol but these season analytes were not detected.

pH

The pH values for each e-liquid correlated with the measured total nicotine concentration (Table 3). In general, college total nicotine concentrations yielded higher pH values due to inherent alkalinity of nicotine. To exam this hypothesis, synthetic e-liquids were prepared using a 1:1 mixture of propylene glycol and glycerin to create e-liquids with nicotine concentrations of 6mg/ml, 11mg/ml, 18mg/ml and 24mg/ml. A series of pH measurements were fabricated on the laboratory prepared e-liquids and a direct relation between total nicotine concentration and pH was observed. When testing the commercial brands of e-liquid, a like correlation between nicotine and pH exists. However, the commercial products contain a number of other flavor additives that could influence the resulting e-liquid pH, thus creating a weaker nicotine/pH relationship in commercial products. Nicotine free due east-liquids were slightly acidic (pH = 5.i–half-dozen.4), perhaps due to the absence of nicotine and the presence of weakly acidic substances.

Table 3.

Nicotine (N = 3), pH (Northward = 2), and Gratuitous-Base Nicotine of Commercial and Laboratory-Prepared Due east-Liquid

Flavor	Nicotine label concentration (mg)	Nicotine (mg/g)	% Difference from label	pH	Free nicotine (%)
South Beach Smoke
Vanilla	0	<LOD	NA	v.3	NA
Tobacco	6	four.five	−25.0	8.3	65.nine
Tobacco Blue	6	four.2	−30.0	7.ix	44.four
Tobacco Aureate	12	9.7	−19.ii	eight.4	68.viii
Peppermint	12	9.2	−23.3	8.seven	81.9
Menthol	16	xiii.1	−18.one	8.v	77.0
Peach	xvi	12.2	−23.viii	8.8	86.3
V2
Menthol	0	<LOD	NA	half-dozen.4	NA
Sahara	vi	five.4	−ten.0	7.8	38.seven
Ruddy	half dozen	5.ix	−1.seven	8.iv	69.vii
Sahara	12	11.0	−eight.3	viii.5	76.half dozen
Peppermint	12	9.6	−20.0	viii.two	62.5
Menthol	18	xv.3	−15.0	8.vii	83.viii
Red	18	16.7	−vii.2	8.9	87.one
Premium
Scarlet	0	<LOD	NA	5.iii	NA
Java	0	<LOD	NA	five.8	NA
Blueberry	6	3.7	−38.three	7.iii	14.seven
Watermelon	half dozen	3.iii	−45.0	7.7	32.9
Pineapple	11	vi.9	−37.3	8.0	48.5
Menthol	eleven	8.5	−22.7	8.8	85.1
Pear	16	x.1	−36.9	eight.2	59.6
Vanilla	sixteen	thirteen.nine	−13.one	8.4	69.5
Tobacco	24	20.5	−14.6	8.9	89.3
Peach	24	xvi.5	−31.iii	8.4	71.7
eSmoke
Morning Coffee	0	<LOD	NA	5.1	NA
Blood-red El Toro	6	6.0	0.0	8.v	76.9
Forenoon Coffee	6	6.1	1.seven	8.four	71.6
Light-green Apple tree	6	6.2	three.3	8.6	79.8
Tobacco RY4	11	xi.3	2.seven	viii.viii	86.1
Minty Menthol	eleven	ten.four	−5.5	8.v	75.8
Caribbean area Coconut	11	xi.1	0.ix	eight.8	86.9
Forenoon Java	11	11.2	i.8	8.seven	82.five
Morning Java	16	16.5	3.1	eight.nine	87.4
MTN Mist	16	16.6	3.8	ix.i	91.7
Laboratory-prepared due east-juice
1:1 PGa/glycerin	0			6.0	NA
	6			9.0	90.five
	xi			9.1	92.9
	16			9.3	94.v
	24			9.3	95.iv

Flavor	Nicotine characterization concentration (mg)	Nicotine (mg/one thousand)	% Difference from label	pH	Free nicotine (%)
Due south Beach Smoke
Vanilla	0	<LOD	NA	5.3	NA
Tobacco	6	four.v	−25.0	8.3	65.9
Tobacco Blueish	6	iv.2	−30.0	7.ix	44.4
Tobacco Gilded	12	nine.7	−19.2	eight.4	68.eight
Peppermint	12	9.2	−23.iii	eight.vii	81.9
Menthol	16	13.1	−xviii.one	8.5	77.0
Peach	xvi	12.ii	−23.8	eight.8	86.3
V2
Menthol	0	<LOD	NA	half dozen.iv	NA
Sahara	6	5.4	−ten.0	7.eight	38.7
Cherry	6	5.9	−i.7	8.iv	69.vii
Sahara	12	eleven.0	−viii.3	8.5	76.6
Peppermint	12	9.6	−20.0	8.2	62.5
Menthol	18	15.3	−fifteen.0	viii.7	83.viii
Red	18	xvi.7	−7.two	8.ix	87.1
Premium
Cerise	0	<LOD	NA	5.iii	NA
Java	0	<LOD	NA	5.8	NA
Blueberry	six	3.7	−38.3	7.3	xiv.7
Watermelon	6	3.three	−45.0	7.vii	32.9
Pineapple	11	6.9	−37.3	eight.0	48.5
Menthol	xi	eight.5	−22.seven	8.8	85.one
Pear	sixteen	10.1	−36.9	eight.two	59.6
Vanilla	sixteen	13.9	−13.1	viii.four	69.5
Tobacco	24	20.v	−14.6	8.9	89.3
Peach	24	xvi.v	−31.3	eight.4	71.7
eSmoke
Morning Coffee	0	<LOD	NA	five.1	NA
Red El Toro	6	6.0	0.0	8.5	76.nine
Morn Coffee	6	6.ane	one.7	8.iv	71.vi
Green Apple	6	6.2	3.3	8.6	79.8
Tobacco RY4	11	11.3	2.7	8.viii	86.i
Minty Menthol	11	10.four	−five.5	8.five	75.eight
Caribbean Coconut	11	11.1	0.9	viii.8	86.9
Forenoon Coffee	11	11.two	ane.8	8.7	82.5
Morning Coffee	16	16.five	3.1	8.9	87.iv
MTN Mist	16	sixteen.6	3.viii	nine.1	91.7
Laboratory-prepared e-juice
ane:1 PGa/glycerin	0			vi.0	NA
	6			9.0	90.5
	eleven			9.one	92.ix
	16			nine.3	94.v
	24			nine.3	95.four

LOD = limit of detection; NA = not applicative.

^aPG = propylene glycol.

Table 3.

Nicotine (N = three), pH (N = 2), and Free-Base Nicotine of Commercial and Laboratory-Prepared Due east-Liquid

Flavor	Nicotine label concentration (mg)	Nicotine (mg/g)	% Difference from characterization	pH	Costless nicotine (%)
South Beach Fume
Vanilla	0	<LOD	NA	v.3	NA
Tobacco	6	four.5	−25.0	viii.3	65.9
Tobacco Blueish	vi	4.2	−30.0	seven.9	44.iv
Tobacco Gold	12	9.vii	−19.2	8.4	68.8
Peppermint	12	ix.ii	−23.3	8.7	81.9
Menthol	16	13.1	−eighteen.1	8.v	77.0
Peach	16	12.ii	−23.8	eight.8	86.3
V2
Menthol	0	<LOD	NA	half dozen.4	NA
Sahara	6	5.four	−10.0	7.viii	38.7
Cherry-red	six	5.ix	−ane.7	8.iv	69.vii
Sahara	12	xi.0	−viii.iii	8.five	76.half-dozen
Peppermint	12	9.six	−20.0	eight.2	62.v
Menthol	18	fifteen.3	−15.0	eight.7	83.8
Red	18	16.7	−7.2	eight.9	87.one
Premium
Cherry	0	<LOD	NA	5.three	NA
Coffee	0	<LOD	NA	5.8	NA
Blueberry	6	3.7	−38.3	7.3	14.7
Watermelon	six	3.3	−45.0	7.vii	32.9
Pineapple	11	vi.ix	−37.3	8.0	48.5
Menthol	11	8.5	−22.7	8.8	85.1
Pear	xvi	ten.i	−36.nine	8.2	59.6
Vanilla	xvi	13.9	−13.1	eight.4	69.v
Tobacco	24	20.five	−14.6	8.nine	89.iii
Peach	24	xvi.5	−31.iii	8.4	71.vii
eSmoke
Morning Coffee	0	<LOD	NA	v.1	NA
Red El Toro	half dozen	half-dozen.0	0.0	8.5	76.nine
Morning Coffee	6	6.one	ane.7	8.four	71.vi
Light-green Apple	6	6.two	3.iii	8.6	79.viii
Tobacco RY4	eleven	11.3	ii.vii	8.8	86.one
Minty Menthol	11	x.4	−v.5	8.5	75.8
Caribbean Coconut	xi	xi.ane	0.9	8.8	86.ix
Morning time Coffee	xi	11.2	ane.viii	8.7	82.5
Morning time Coffee	16	16.5	3.1	8.9	87.4
MTN Mist	16	xvi.6	3.8	ix.1	91.7
Laboratory-prepared e-juice
1:1 PGa/glycerin	0			6.0	NA
	6			9.0	ninety.5
	11			9.1	92.9
	xvi			ix.3	94.5
	24			ix.3	95.4

Flavor	Nicotine label concentration (mg)	Nicotine (mg/g)	% Deviation from label	pH	Complimentary nicotine (%)
South Beach Smoke
Vanilla	0	<LOD	NA	5.iii	NA
Tobacco	6	4.5	−25.0	8.3	65.ix
Tobacco Blue	half dozen	iv.2	−xxx.0	vii.9	44.4
Tobacco Golden	12	9.7	−19.2	8.four	68.eight
Peppermint	12	9.2	−23.3	8.7	81.9
Menthol	16	13.ane	−18.1	8.5	77.0
Peach	16	12.2	−23.8	8.eight	86.three
V2
Menthol	0	<LOD	NA	6.4	NA
Sahara	6	v.4	−10.0	7.8	38.7
Carmine	half-dozen	5.ix	−1.7	8.4	69.7
Sahara	12	11.0	−8.3	8.v	76.six
Peppermint	12	9.half-dozen	−20.0	8.2	62.v
Menthol	18	15.3	−15.0	eight.7	83.8
Red	xviii	16.7	−7.2	8.9	87.1
Premium
Cherry	0	<LOD	NA	5.3	NA
Coffee	0	<LOD	NA	five.eight	NA
Huckleberry	6	3.seven	−38.3	7.iii	14.vii
Watermelon	6	3.iii	−45.0	7.vii	32.9
Pineapple	11	half dozen.9	−37.3	8.0	48.5
Menthol	11	8.5	−22.7	8.viii	85.1
Pear	sixteen	x.1	−36.9	8.2	59.6
Vanilla	16	xiii.9	−xiii.ane	8.iv	69.five
Tobacco	24	xx.5	−fourteen.6	8.9	89.iii
Peach	24	16.5	−31.three	eight.four	71.seven
eSmoke
Morn Coffee	0	<LOD	NA	v.1	NA
Cherry El Toro	half dozen	6.0	0.0	8.5	76.9
Morning Coffee	half-dozen	half-dozen.1	1.7	eight.4	71.6
Dark-green Apple tree	6	six.2	iii.3	8.6	79.eight
Tobacco RY4	eleven	11.iii	2.7	viii.8	86.1
Minty Menthol	11	10.4	−5.5	8.5	75.8
Caribbean Coconut	11	11.i	0.9	8.viii	86.9
Morning Coffee	xi	eleven.two	one.8	8.7	82.five
Morning Coffee	sixteen	16.5	3.i	8.9	87.4
MTN Mist	16	16.6	3.8	nine.1	91.7
Laboratory-prepared due east-juice
1:1 PGa/glycerin	0			6.0	NA
	6			9.0	90.5
	11			9.1	92.9
	xvi			9.3	94.5
	24			9.iii	95.four

LOD = limit of detection; NA = non applicative.

^aPG = propylene glycol.

The percentage of nicotine in the free (unprotonated) grade can be calculated using the Henderson-Hasselbach equation based on measured pH and total nicotine. ³² The free or unprotonated form of nicotine is more readily absorbed past the user than protonated forms, increasing the rate of uptake of nicotine received by the user. ⁴¹ More often than not, all due east-liquids that contained nicotine had free-base nicotine concentrations in the range of lx%–90%, and there was a trend toward increasing complimentary-base nicotine concentrations as the measured full nicotine concentrations increased. Considering it was adamant that the pH is driven by the alkalinity of nicotine in laboratory prepared e-liquids, this observation was expected (Figure ii). The correlation between pH, measured nicotine and free-base nicotine is not as strong (R ² = 0.827 for commercial products vs. R ² = 0.965 for laboratory prepared e-liquids), likely due to flavors and other additives establish in the various due east-liquids. For the nicotine-containing products tested, the gratuitous-base nicotine percentages plateaued at approximately xc%.

Figure two.

Comparison of measured nicotine and complimentary base nicotine for commercial and synthetic east-juice point nicotine's alkalinity drives pH and the subsequent free-nicotine (%) levels. A logarithmic fit was chosen based on the characteristics of the Henderson-Hasselbach equation.

Figure 2.

Comparing of measured nicotine and free base nicotine for commercial and synthetic e-juice bespeak nicotine's alkalinity drives pH and the subsequent free-nicotine (%) levels. A logarithmic fit was chosen based on the characteristics of the Henderson-Hasselbach equation.

Give-and-take

We evaluated pH, nicotine, flavors, and minor tobacco alkaloids in e-liquid plant in cartridges and refill solutions of four e-cigarette manufacturers: South Beach Smoke, Premium, V2, and eSmoke. The measured nicotine levels for South Beach Smoke, Premium and V2 were all significantly lower than the labeled concentrations. Because labels are inaccurate, an inherent consumer risk exists in that consumers do non know how much nicotine they may be exposed to when using e-cigarettes. Although results from this study institute measured nicotine levels lower than labeled concentrations, other studies accept found more than nicotine than labeled concentrations. ^17–26 Regardless of the inaccuracies on the label, most of the e-liquids tested had a high pct (60%–ninety%) of nicotine existing in free or unprotonated grade. The amount of nicotine in eastward-liquids tin can result in adverse medical effects if ingested ⁴² and as a result, calls to poison command centers nearly exposures to e-cigarette products have increased dramatically. ⁴³ Minor tobacco alkaloids were constitute in all nicotine containing e-liquid varieties, which suggests the nicotine in the e-liquids is extracted from tobacco. In some cases, minor alkaloid levels indicate that the nicotine used in certain east-liquids exceeded USP impurity specifications. The limitation of this observation is that the oxidation rate of nicotine is unknown, thus the source of impurities cannot be identified with certainty. Products from all four manufacturers tested independent measureable levels of flavors. Flavors accept been shown to play an important role in helping enhance the experience for the east-cigarette user, as well as potentially aiding with smoking abstinence. ^44,45 Although flavored e-cigarette products are popular with adult users, sweet and candy-similar flavors may make e-cigarettes attractive to children. ⁴⁶ The pH of eastward-liquids that were examined was largely driven by the concentration of nicotine due to its alkalinity. A direct correlation was found between pH, measured total nicotine concentration, and complimentary nicotine (%) in e-liquids.

This enquiry assessed unmarried manufacturer lots of 36 unlike e-liquids from iv manufacturers; much more research is needed to more fully characterize e-cigarettes and assess potential public wellness concerns resulting from increased use of e-cigarettes and other electronic nicotine commitment devices. Our evaluation of the due east-liquids provides insight into constituents and additives in current brands, but given the number of brands and the dynamic market, and we believe routine belittling testing of products is warranted.

Supplementary Textile

Supplementary Tables 1 and 2 and Effigy 1 tin can be found online at http://www.ntr.oxfordjournals.org

Funding

Funding was provided internally through the Centers for Disease Command and Prevention .

Declaration of Interests

None declared.

Acknowledgments

The findings and conclusions in this written report are those of the authors and do non necessarily stand for the views of the Centers for Disease Control and Prevention. This information is distributed solely for the purpose of pre dissemination peer review under applicative information quality guidelines. It has not been formally disseminated by the Centers for Affliction Control and Prevention. It does not represent and should non be construed to represent any bureau decision or policy.

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© Published past Oxford Academy Press on behalf of the Order for Research on Nicotine and Tobacco 2015. This work is written past (a) US Government employee(s) and is in the public domain in the U.s..

What Is The Chemical Makeup Of Nicotine,

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