Carboxylate Counteranions in Electronic Cigarette ... - ACS Publications

Subscriber access provided by UNIV OF NEWCASTLE

Article

Carboxylate counter anions in electronic cigarette liquids: Influence on nicotine emissions Ahmad El Hellani, Rachel El-Hage, Rola Salman, Soha Talih, Alan Shihadeh, and Najat Aoun Saliba Chem. Res. Toxicol., Just Accepted Manuscript • DOI: 10.1021/acs.chemrestox.7b00090 • Publication Date (Web): 07 Jul 2017 Downloaded from http://pubs.acs.org on July 13, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Chemical Research in Toxicology is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 21

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chemical Research in Toxicology

Carboxylate counter anions in electronic cigarette liquids: Influence on nicotine emissions Ahmad EL-Hellani, PhD,†,§ Rachel El-Hage, MS,†,§ Rola Salman, BS,‡,§ Soha Talih, PhD,‡,§ Alan Shihadeh, ScD,‡,§ and Najat A. Saliba, PhD,†,§,* † American University of Beirut, Lebanon, Chemistry Department, Faculty of Arts and Sciences, 1107 2020, Lebanon ‡ American University of Beirut, Lebanon, Mechanical Engineering Department, Faculty of Engineering and Architecture, 1107 2020, Lebanon § Center for the Study of Tobacco Products, Virginia Commonwealth University, Richmond, Virginia 23284, USA

* Corresponding Author: Najat A. Saliba, Mailing address: American University of Beirut, Bliss Street, P.O. Box 11-0236, Riyad El-Solh, Beirut 1107 2020, Lebanon. Tel: +961 1 350000/3992 E-mail: [email protected].

1 ACS Paragon Plus Environment


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Keywords electronic cigarette, nicotine, counter anion, carboxylate, and aerosol. Abstract The wide pH range reported for electronic cigarette (ECIG) liquids indicates that nicotine may be present in one or more chemical forms. The nicotine form affects the bioavailability and delivery of nicotine from inhaled products. Protonated nicotine are normally associated with counter anions in tobacco products. The chemical and physical properties of counter anions may differently influence the nicotine form and emissions in ECIG aerosols. In this study, we examined how these anions influence nicotine emissions as well as their evaporation behavior and potential decomposition during ECIG operation. ECIG liquid solutions with equal nicotine concentration and pH but different counter anions (formate, acetate, and citrate) were prepared from analytical standards to assess the effect of the counter anion on nicotine partitioning. High performance liquid and gas chromatography methods were developed to determine the counter anions and the two protonated (NicH+) and free base (Nic) forms of nicotine in commercially available and standard solutions of ECIG liquids and aerosols. In commercial samples, acetate and citrate anions were detected. In standard solutions, both formate and acetate ions were found to evaporate intact but citrate ion decomposed into formic acid and other products. This study also shows that the identity of the counter anion has no effect on total nicotine emission from ECIG in agreement with previous reports on tobacco cigarettes. However, the partitioning of aerosolized nicotine into NicH+ and Nic is aniondependent even when the parent liquid pH is held constant. These results indicate that the anions found in a given ECIG product may influence the nicotine delivery profile to the user by enriching aerosols with free-base nicotine as in the case of poly-carboxylic acids such as citric acid.


Page 2 of 21

Page 3 of 21

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


I. Introduction Worldwide electronic cigarette (ECIG) popularity is partially attributed to their ability to deliver nicotine to the bloodstream in comparable levels to combustible cigarettes.1-5 Different ECIG device and e-liquid characteristics, coupled to user behavior, can influence nicotine delivery by affecting the amount of nicotine emitted by the device as well as the relative proportion of nicotine found in the free-base form (Nic).6-9 The Nic fraction in the aerosol was recently shown to be dictated by the fraction of Nic in the e-liquid10 suggesting that even when the nicotine concentration is held constant, ECIG liquids with different pHs (4.8-9.6)11 may widely vary in their ability to deliver nicotine systemically. This is due to free-base nicotine being the bioavailable form of nicotine as reported in the literature. Nicotine can exist in one of three forms depending on the protonation of its nitrogen centers: Nic, mono-protonated salt (NicH+, X-), or di-protonated salt (NicH22+, 2X-). Nicotine salts in tobacco leaves consist of protonated nicotine bound to organic counter anions (X-)- mainly mono- or poly-carboxylates.12 Nicotine in ECIG liquids usually come from the extraction of tobacco leaves,13 and this may be the main source of poly-carboxylate anions like citrate or tartrate. However, mono-carboxylate anions such as formate and acetate are expected to be present if the extraction process includes an acidification step using a carboxylic acid.14 Therefore, we hypothesize that nicotine delivery from ECIG emissions may vary even when the parent liquids have the same pH depending on the identity of the counter anion found in the liquid.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Although Nic is the only volatile form, NicH+ was detected in both tobacco cigarette smoke and ECIG vapor.10,14-17 Assessing the parameters that affect NicH+ aerosolization is very important because nicotine delivery to the body is usually linked to nicotine forms.18 Therefore, this work is complementary to our prior study that addressed the effect of the Nic/NicH+ ratio in ECIG liquids on total nicotine yield and Nic/NicH+ ratio in the aerosol,10 However, our goal here is to study the effect of the counter anion on these two measurements. We identify the counter anions in some of the commercial ECIG brands and assess the effect of the counter anion using standard solutions. We then measure the total and fraction of free base nicotine as well as the acid content in aerosols.

II. Materials and Methods II.1. Materials ECIGs of EC-Blend, Retro, Blu and Liquid Express brands were procured from internet vendors. High Performance Liquid Chromatography (HPLC)-grade water, toluene and acetonitrile solvents, pure free-base nicotine (CAS registry number 54-11-5) and hexadecane (CAS registry number 544-76-3) were procured from Sigma Aldrich. The latter was used as an internal standard in nicotine quantification. Formic (CAS registry number 64-18-6), acetic (CAS registry number 64-19-7), tartaric (CAS registry number 87-69-4) and citric acids (CAS registry number 5949-29-1) were procured from Sigma Aldrich and Surechem products Ltd. Quartz filters (47 mm diameter) were purchased from Whatman International Ltd. and used for particle phase trapping. 4 ACS Paragon Plus Environment

Page 4 of 21

Page 5 of 21

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


II.2. pH measurements of commercial ECIG liquid solutions Depending on the labeled nicotine concentration, 0.15-0.45 mL of ECIG liquid was added to deionized water in order to prepare a final solution 6 mL of 600 µg/mL nicotine concentration in a final volume of 6 mL. The pH of this extract was measured by a Starter 3100 OHAUS pHmeter. II.3. Determination of the counter anion The counter anion of protonated nicotine in commercial products was determined by high performance liquid chromatography-diode array detection (HPLC-DAD). Formic, acetic, tartaric and citric solutions were used as standards. ECIG liquid solution at 800 µg/mL was prepared by dissolving an X mL (depending on the nicotine labelled concentration) of ECIG liquid in 1 mL of water as a function of its stock concentration (e.g. 50 µL of ECIG liquid of nicotine concentration of 16 mg/mL was dissolved in 1 mL of water). The resulting solution was sonicated for 30 min, and then a 15 µL aliquot was injected into an Agilent 1100 HPLC-DAD system, equipped with Bio wide pore C18-5 column (25 cm × 4.6 mm, 5 µm) purchased from Supelco. An isocratic elution using a mixture of 97 % sulfuric acid solution (0.05 % v/v aqueous solution) and 3 % acetonitrile (pH = 2.7) was run at 0.4 mL/min. Formic, acetic, tartaric and citric acid were detected at 210 nm and at 9.3, 11.2, 8.8 and 12.1 min, respectively. The acid content was confirmed by comparison to standard solutions or by standard addition to the samples when necessary. For quantification, calibration curves for the different acids were prepared. II.4. Lab prepared standard ECIG liquid solutions



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The nicotine-counter anion solutions were prepared by drop-wise addition of standard solutions of formic, acetic and citric solutions to basic nicotine solutions of 36 µg/mL in propylene glycol (PG) in order to reach a final pH of 8. The final pHs of the nicotine-formate, nicotine-acetate and nicotine-citrate were 7.9, 8.2 and 8.0, respectively. Samples of two monocarboxylic acids, i.e. formic acid (boiling points (bp) of 100.8 °C) and acetic acid (bp of 118 °C) and one polycarboxylic acid (citric acid with bp of 310 °C) were used to assess their effect on nicotine evaporation and elucidate the mechanism of evaporation. Citric acid is also thermally unstable, since it starts degrading at relatively low temperatures (< 200 °C). II.5. Aerosol generation and sampling A custom-designed digital puff production machine was used to generate ECIG aerosols from a session of 15 puffs at two different powers (1.30 ± 0.05 and 4.65 ± 0.17 W).6 Puff topography (puff duration, inter-puff interval, and flow rate) was selected to represent an experienced ECIG user with a rectangular shape puff volume of 67 mL, 4 s puff duration, 10 s inter-puff duration, a puff velocity of 1 L/min.6 Two branches emerged from the ECIG mouthpiece: total particulate matter (TPM) in one branch was collected on a quartz filter for nicotine quantification, and TPM in the other branch was collected on another quartz filter for determination of the counter anion. Each sample was tested in triplicates and the results are shown as the average of three measurements. The TPM was determined gravimetrically by weighing the filter pad before and after each sampling session. II.6. Nicotine quantification and partitioning in ECIG liquid and aerosol


Page 6 of 21

Page 7 of 21

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


NicH+ and Nic were quantified according to a reported method (NicH22+ is not present in the prepared solutions at pH around 8).10 In brief, an aliquot of ECIG liquid was immersed in 6 mL of water to form a solution of 600 µg/mL concentration, and then 6 mL of toluene were added to extract Nic from the aqueous phase. This step was repeated to ensure complete extraction of Nic. Next, 700 μL of NaOH solution (1N) was added to the aqueous layer to convert NicH+ in solution into Nic, before extracting the solution twice with toluene as described for the Nic fraction. Toluene extracts were diluted before injection into the Gas Chromatograph (GC-FID) for analysis. Quantification was done using a calibration curve (50-1000 µg/mL) prepared from standard nicotine solutions. Similarly, nicotine forms were separately quantified in the aerosol using the same method by immersing the filter pad in 6 mL of water and following the same steps. The oven temperature program of GC-FID was initiated at 70 ˚C for 2 min and then ramped at 25 ˚C/min until reaching 220 ˚C, and held for 1 min, the total run time was 9 min. III. Results Acetate and citrate anions were identified in some of the tested commercial ECIG liquids (Table 1). Accordingly, the standard solutions of nicotine-acetate, -citrate and -formate (the most volatile) were tested in order to assess the effect of the counter anion on nicotine emissions. The ECIG was run at 1.3 W and 4.6 W to assess the effect of the battery power output on the status of the anion species. Starting with the same liquid nicotine concentration, we found that the aerosol nicotine concentration at 1.3 W (14.9 ± 1.9 mg/mL) was smaller than that at 4.6 W (25.3 ± 0.9 mg/mL). Both were lower than the initial concentration in the ECIG liquid (35.8 ± 0.2



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

mg/mL) (significant difference with P < 0.01) as shown in Figure 1. At a given power, the total nicotine yields in aerosols generated from formic, acetic or citric ECIG liquids were not significantly different. In terms of free-base nicotine (Nic) however, the Nic fraction in aerosols formed from heating formic and acetic acid solutions at 1.3 and 4.6 W (Figure 2) were similar to those in the liquid. The citric acid solution had significantly higher aerosol Nic fraction at 1.3 and 4.6W than its corresponding liquid solution. It is important to note that low citric acid concentrations were detected in aerosols as shown in Figure 3. Discussion This study assesses the effect of the counter anion of protonated nicotine in ECIG liquids on the delivery of total and free base nicotine to the aerosol. The results showed that total nicotine yield in the aerosol is independent of the nature of the counter anion, and the efficiency of nicotine transfer to aerosols was similar between free-base nicotine and nicotine salt solutions. These findings support what was reported by Shihadeh and coworkers who showed that the total nicotine yield obtained from e-cigarettes is independent of pH and is mainly a function of the total nicotine content in ECIG liquid and the battery power output.6,7,10,19 This also agrees with the literature on tobacco cigarettes where nicotine vaporization efficiency is the same regardless of the nicotine source (i.e. tobacco leaves), its protonation with various acids, or its presence in the free-base form.14,16 The observation that nicotine concentrations in aerosols were lower than in ECIG liquids is attributed to the lower vapor pressure of PG compared to nicotine as described by Talih et al.20


Page 8 of 21

Page 9 of 21

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


The distribution between NicH+ and Nic in aerosols was similar to that in ECIG liquids for the highly volatile mono-carboxylic acids (formic and acetic) at both powers. Hellani et al. reported similar results for e-liquid solutions that were prepared with highly volatile acids like acetic acid.10 However, in the case of low volatile poly-carboxylic acids like citric acid, the results showed that the aerosol was enriched with Nic at both power outputs. The higher Nic concentrations in aerosols can be attributed to the inability of citric acid to evaporate at lower power (1.3 W) or the anion degradation because formic acid was detected in the aerosols at 4.6 W.21 In conformity, citric acid was recently shown to degrade under normal ECIG operation conditions.22 Two pathways for nicotine evaporation from nicotine salts into the particle phase have been suggested.14,16 First the evaporation of NicH+ during vaping is initiated by the dissociation of Nic-H+,X-. The volatile Nic and HX products (formic and acetic acids), re-combine in the particle phase to form NicHX (formate and acetate) salts. Second, the partial thermal decomposition of the polycarboxylic acid (citric acid) occurs via dehydration and/or decarboxylation, and the Nic is released to the aerosol. Hence, the counter anion of the protonated nicotine salts does not influence the total nicotine yield and consequently the nicotine flux,19 but determines the Nic/NicH+ distribution in the aerosol. The variation in the Nic fraction in aerosols affects the nicotine delivery to the different absorption sites in the human respiratory tract, and impacts the systemic delivery.18 Conclusion



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 21

The total nicotine yield in aerosols is mainly a function of the power output. It is independent of the identity of the counter ion that is bound to the protonated nicotine in liquid ECIG. At a given pH, the partitioning of aerosolized nicotine into NicH+ and Nic is similar to that in the ECIG liquids when the counter carboxylate ion is thermally stable and able to evaporate at the ECIG operating temperatures, i.e. formic and acetic acids vaped at 1.3 and 4.6 W. Aerosols become enriched with Nic when they contain thermally unstable carboxylate ions like citric acid. The results indicate that the counter anions of protonated nicotine salts in ECIG products play a role in the delivery profile of nicotine to the user by altering the Nic/NicH+ ratio in the aerosol. Funding Sources Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number P50DA036105 and the Center for Tobacco Products of the U.S. Food and Drug Administration.

Declaration of interests The authors have no conflicts of interest to report.

Acknowledgment The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.

Abbreviation


Page 11 of 21

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


ECIG: electronic cigarette, Nic: free-base nicotine, NicH+: protonated nicotine, NicH22+: diprotonated nicotine, HPLC-DAD: high performance liquid chromatography-diode array detection, GC-FID: gas chromatography-flame ionization detector, TSNAs: tobacco-specific nitrosoamines.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

References 1.

2. 3. 4. 5.

6.

7.

8.

9.

10.

11. 12. 13.

14.

15.

16.

Ramôa C. P., Hiler M. M., Spindle T. R., Lopez A. A., Karaoghlanian N., Lipato T., Breland A. B., Shihadeh A., Eissenberg T. (2016) Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: A preliminary report. Tob. Control. 25, e6-e9. Hajek P., Przulj D., Phillips A., Anderson R., McRobbie H. (2017) Nicotine delivery to users from cigarettes and from different types of e-cigarettes. Psychopharmacology. 234, 773-779. Schroeder M. J., Hoffman A. C. (2014) Electronic cigarettes and nicotine clinical pharmacology. Tob. Control. 23, ii30-ii35. Vansickel A. R., Eissenberg T. (2012) Electronic cigarettes: Effective nicotine delivery after acute administration. Nicotine Tob. Res. 15, 267-270. Yan X. S., D’Ruiz C. (2015) Effects of using electronic cigarettes on nicotine delivery and cardiovascular function in comparison with regular cigarettes. Regul. Toxicol. Pharmacol. 71, 2434. Talih S., Balhas Z., Eissenberg T., Salman R., Karaoghlanian N., El-Hellani A., Baalbaki R., Saliba N., Shihadeh A. (2015) Effects of user puff topography, device voltage, and liquid nicotine concentration on electronic cigarette nicotine yield: Measurements and model predictions. Nicotine Tob. Res. 17, 150-157. EL-Hellani A., Salman R., El-Hage R., Talih S., Malek N., Baalbaki R., Karaoghlanian N., Nakkash R., Shihadeh A., Saliba N. A. (2016) Nicotine and carbonyl emissions from popular electronic cigarette products: correlation to liquid composition and design. Nicotine Tob. Res., DOI: https://doi.org/10.1093/ntr/ntw1280. Farsalinos K. E., Spyrou A., Tsimopoulou K., Stefopoulos C., Romagna G., Voudris V. (2014) Nicotine absorption from electronic cigarette use: comparison between first and newgeneration devices. Sci. Rep. 4, 4133. Farsalinos K. E., Spyrou A., Stefopoulos C., Tsimopoulou K., Kourkoveli P., Tsiapras D., Kyrzopoulos S., Poulas K., Voudris V. (2015) Nicotine absorption from electronic cigarette use: comparison between experienced consumers (vapers) and naïve users (smokers). Sci. Rep. 5, 11269. El-Hellani A., El-Hage R., Baalbaki R., Salman R., Talih S., Shihadeh A., Saliba N. A. (2015) Freebase and protonated nicotine in electronic cigarette liquids and aerosols. Chem. Res. Toxicol. 28, 1532-1537. Stepanov I., Fujioka N. (2015) Bringing attention to e-cigarette pH as an important element for research and regulation. Tob. Control. 24, 413-414. Perfetti T. (1983) Structural study of nicotine salts. Beit. Tab. Int. 12, 43-54. Farsalinos K., Gillman I., Melvin M., Paolantonio A., Gardow W., Humphries K., Brown S., Poulas K., Voudris V. (2015) Nicotine levels and presence of selected tobacco-derived toxins in tobacco flavoured electronic cigarette refill liquids. Int. J. Environ. Res. Public Health. 12, 3439-3452. Seeman J. I., Fournier J. A., Paine J. B., Waymack B. E. (1999) The form of nicotine in tobacco. Thermal transfer of nicotine and nicotine acid salts to nicotine in the gas phase. J. Agric. Food Chem. 47, 5133-5145. Pankow J. F., Tavakoli A. D., Luo W., Isabelle L. M. (2003) Percent free base nicotine in the tobacco smoke particulate matter of selected commercial and reference cigarettes. Chem. Res. Toxicol. 16, 1014-1018. Perfetti T., Norman A., Gordon B., Coleman III W., Morgan W., Dull G., Miller C. (2000) The transfer of nicotine from nicotine salts to mainstream smoke. Beitr. Tab. Int. 19, 141-158.


Page 12 of 21

Page 13 of 21

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


17.

18. 19. 20.

21. 22.

Pankow J. F. (2001) A consideration of the role of gas/particle partitioning in the deposition of nicotine and other tobacco smoke compounds in the respiratory tract. Chem. Res. Toxicol. 14, 1465-1481. Caldwell B., Sumner W., Crane J. (2012) A systematic review of nicotine by inhalation: Is there a role for the inhaled route? Nicotine Tob. Res. 14, 1127-1139. Shihadeh A., Eissenberg T. (2015) Electronic cigarette effectiveness and abuse liability: Predicting and regulating nicotine flux. Nicotine Tob. Res. 17, 158-162. Talih S., Balhas Z., Salman R., El-Hage R., Karaoghlanian N., El-Hellani A., Baassiri M., Jaroudi E., Eissenberg T., Saliba N., Shihadeh A. (2017) Transport phenomena governing nicotine emissions from electronic cigarettes: Model formulation and experimental investigation. Aerosol Sci. Technol. 51, 1-11. Wyrzykowski D., Hebanowska E., Nowak-Wiczk G., Makowski M., Chmurzyński L. (2011) Thermal behaviour of citric acid and isomeric aconitic acids. J. Therm. Anal. Calorim. 104, 731-735. Costigan S. (2017) Citric acid has the potential to produce respiratory sensitisers in e-cigarette vapor. https://www.eurekalert.org/pub_releases/2017-2003/raba-cah030917.php.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 21

Table 1. Identification of counter anion of protonated nicotine in some commercial e-liquid solutions Brand

Flavor

Liq conc (mg/mL)

pH

Counter anion

EC-blend

Buttered Keoke rum coffee

18

5.5

Acetate

Blu

Classic

24

7.7

Acetate

Retro

Citrus fizz

6

9.0

Acetate

Retro

Juggle bear

18

7.0

Acetate

Liquid express

Watermelon chill

26

9.1

Citrate


Page 15 of 21

40 Liq 1.3 W 4.6 W

35

30 Nicotine concentration (mg/mL)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


**

**

**

**

25

**

20 **

** **

15

10

5

0 Free-base

Formic

Acetic

Citric

Figure 1. Total nicotine concentration in ECIG liquid compared to nicotine concentration in the aerosol (yield) generated at 1.3 and 4.6 W. Significant difference (**: P < 0.01) of aerosol relative to liquid; signiﬁcant diﬀerence (‡: P < 0.01) of acid ECIG liquids relative to free-base liquid. A significant difference (P < 0.01) was also found between 1.3 and 4.6 W for all ECIG liquids



100 ** *

Liq 1.3 W 4.6 W

80

60 Nic fraction

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 21

40

20

0 Free-base

Formic

Acetic

Citric

Figure 2. Comparison of Nic fraction in the aerosols generated at 1.3 and 4.6 W to that in the corresponding e-liquid. Significant difference (*: P < 0.1, **: P < 0.01) relative to the parent liquid


Page 17 of 21

10

Liq 1.3 W 4.6 W

8

Acid concentration (mg/mL)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


6

4

2

0 Formic Acid

Acetic Acid

Citric Acid

Figure 3. Concentrations of formic, acetic and citric acid in the ECIG liquid solutions and in aerosols generated at 1.3 and 4.6 W


40

Nicotine concentration (mg/mL)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39


Page 18 of 21

Liq 1.3 W 4.6 W

35

30

**

**

**

**

25 **

20 **

** **

15

10

5

0

Free-base

FormicACS Paragon Plus Environment Acetic

Citric

Page100 19 of 21


** * 80

60

Nic fraction

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39

40

20

0

Free-base

Formic Acetic ACS Paragon Plus Environment

Citric

Liq 1.3 W 4.6 W

10

Acid concentration (mg/mL)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39


Page 20 of 21

Liq 1.3 W 4.6 W

8

6

4

2

0

Formic Acid

Acetic Acid ACS Paragon Plus Environment

Citric Acid

Page 21 of 21


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Paragon Plus Environment

Carboxylate Counteranions in Electronic Cigarette ... - ACS Publications

Recommend Documents