An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids

In electronic cigarette users, nicotine delivery to lungs depends on various factors. One of the important factors is e-liquid nicotine concentration. Nicotine concentration in e-liquids ranges from 0 to \u3e50 mg/mL. Furthermore, nicotine exists in protonated and unprotonated (“free base”) forms. The two forms are believed to affect the nicotine absorption in body. Therefore, in addition to total nicotine concentration, e-liquids should be characterized for their free base nicotine yield. Two approaches are being used for the determination of free base nicotine in e-liquids. The first is applying a dilution to e-liquids followed by two methods: Henderson–Hasselbalch theory application or a Liquid-Liquid Extraction. The second is the without-dilution approach followed by 1H NMR method. Here, we carried out controlled experiments using five e-liquids of different flavors using these two approaches. In the dilution approach, the Henderson–Hasselbalch method was tested using potentiometric titration. The accuracy was found to be \u3e98% for all five e-liquid samples (n = 3). A Liquid-Liquid Extraction was carried out using toluene or hexane as extraction solvent. The Liquid-Liquid Extraction technique was found to be limited by solvent interactions with flavors. Solvent extractions resulted in flavor dependent inaccuracies in free base nicotine determination (5 to 277% of calculated values). The without-dilution approach was carried out using 1H NMR as described by Duell et al. This approach is proposed to offer an independent and alternative scale. None of the methods have established a strong correlation between pre- and postvaporization free base nicotine yield. Here we present comparative results of two approaches using analytical techniques. Such a comparison would be helpful in establishing a standardized method for free base nicotine determination of e-liquids

Storungen des Eiweiss- und Mineralhaushalts sowie einiger Enzyme bei akuter experimenteller Kadmiumvergiftung

Na kunićima, koji su nekoliko dana trovani kadmijevim kloridom, mjerena je promjena koncentracije bjelančevina, minerala i enzima u krvnom serumu, zatim je određena promjena koncentracije glutationa u eritrocitima i promjene aktivnosti alanini asparagin-aminoferaze i kolinesteraze u homogenatima jetre, bubrega, pluća i mozga. Nakon 10 dana trovanja smanjila se je koncentracija albumina, a povećala koncentracija globulina, naročito ß-frakcije. Od lipoproteina smanjila se koncentracija a-frakcije, a povećala ß-frakcija; kolesterol vezan uz ß-frakciju se utrostručio. Koncentracija kalija i kalcija u serumu bila je povećana. Aktivnost alanin- i asparagin aminoferaze i kolinesteraze povećala se u serumu, jetri i bubrezima. Količina reduciranog glutationa ostala je gotovo nepromijenjena u eritrocitima, ali se je povećala u jetri. Akutno trovanje kadmijem uzrokuje oštećenje bubrega praćeno povećanjem koncentracije mokraćne kiseline i kreatinina. Najveće promjene primijećene su u organima koji kumuliraju kadmij, a to su jetra i bubrezi.Bei mit Kadmiumchlorid 10 Tage hindurch vergifteten Kaninchen wurden folgende Daten untersucht: Eiweiss-, Mineral- und Enzymveränderungen im Blutserum, der Gehalt des reduzierten Glutathion in den Erythrozyten sowie Aktivitätsveränderungen der Alanin- Asparaginaminopherase und Cholinesterase in den Leber-, Nieren-, Lungen- und Hirnhomogenaten. Die Ergebnisse zeigten nach 10 tägiger Vergiftung mit Massivdosen von CdCl2 eine Abnahme der Albumine und Anstieg der Globuline, besonders der ß-Fraktion. Im Lipoproteinbild verminderte sich die a-Fraktion und vermehrte sich die ß-Fraktion, das mit ihr verbundene Cholesterol, stieg insgesamt um das Dreifache. Der K- und Ca- Spiegel im Serum stieg an. Die Aktivität der Alanin- und Asparaginaminopherase sowie Cholinesterase wuchs nach der Vergiftung im Blutserum und in den Geweben besonders in Leber und Nieren an. Der Gehalt des reduzierten Glutathion zeigte in den Erythrozyten keine wesentlichen Unterschiede, in der Leber dagegen eine Steigerung. Akute Kadmiumvergiftung ruft Nierenschädigung mit einer Erhöhung des Harnsäure und Kreatininspiegels hervor. Die grössten Veränderungen wurden in kadmiumkumulierenden Organen (Leber und Nieren) beobachtet

The Effect of Electronic Cigarette User Modifications and E-liquid Adulteration on the Particle Size Profile of an Aerosolized Product

Electronic cigarettes (e-cigarettes) are an alternate nicotine delivery system that generate a condensation aerosol to be inhaled by the user. The size of the droplets formed in the aerosol can vary and contributes to drug deposition and ultimate bioavailability in the lung. The growing popularity of e-cigarette products has caused an increase in internet sources promoting the use of drugs other than nicotine (DOTNs) in e-cigarettes. The purpose of this study was to determine the effect of various e-cigarette and e-liquid modifications, such as coil resistance, battery voltage, and glycol and drug formulation, on the aerosol particle size. E-liquids containing 12 mg/mL nicotine prepared in glycol compositions of 100% propylene glycol (PG), 100% vegetable glycerin (VG), or 50:50 PG:VG were aerosolized at three voltages and three coil resistances. Methamphetamine and methadone e-liquids were prepared at 60 mg/mL in 50:50 PG:VG and all e-liquids were aerosolized onto a 10 stage Micro-Orifice Uniform Deposit Impactor. Glycol deposition correlated with drug deposition, and the majority of particles centered between 0.172–0.5 μm in diameter, representing pulmonary deposition. The 100% PG e-liquid produced the largest aerosol particles and the 100% VG and 50:50 PG:VG e-liquids produced ultra-fine particles \u3c0.3 μm. The presence of ultrafine particles indicates that drugs can be aerosolized and reach the pulmonary alveolar regions, highlighting a potential for abuse and risk of overdose with DOTNs aerosolized in an e-cigarette system

The time course of compensatory puffing with an electronic cigarette: Secondary analysis of real-world puffing data with high and low nicotine concentration under fixed and adjustable power settings

Introduction: In a secondary analysis of our published data demonstrating compensatory vaping behavior (increased puff number, puff duration, and device power) with e-cigarettes refilled with low versus high nicotine concentration e-liquid, here we examine 5-day time course over which compensatory behavior occurs under fixed and adjustable power settings. Aims and Methods: Nineteen experienced vapers (37.90 ± 10.66 years, eight females) vaped ad libitum for 5 consecutive days under four counterbalanced conditions (ie, 20 days in total): (1) low nicotine (6 mg/mL)/fixed power (4.0 V/10 W); (2) low nicotine/adjustable power; (3) high nicotine (18 mg/mL)/fixed power; (4) high nicotine/adjustable power (at 1.6 Ohm). Puff number, puff duration, and power settings were recorded by the device. For each day, total daily puffing time was calculated by multiplying daily puff number by mean daily puff duration. Results: A significant day × setting interaction revealed that whilst puffing compensation (daily puffing time) continued to increase over 5 days under fixed power, it remained stable when power settings were adjustable. Separate analysis for puff number and puff duration suggested that the puffing compensatory behavior was largely maintained via longer puff duration. Conclusions: Under fixed power conditions (4.0 V/10 W), vapers appear to compensate for poor nicotine delivery by taking longer puffs and this compensatory puffing appears to be maintained over time. Implications: Studies in smokers suggest that when switching to lower nicotine levels, compensation for poorer nicotine delivery is transient. Our novel findings suggest that vapers show a different pattern of compensation which is influenced by both nicotine strength and device power settings. When power is fixed (4.0 V; 10 W), compensation (via more intensive puffing) appears prolonged, persisting up to 5 days. Under adjustable settings when power is increased, puffing patterns remain stable over time. Implications of such compensatory behaviors for product safety and user satisfaction need further exploration

Daily exposure to formaldehyde and acetaldehyde and potential health risk associated with use of high and low nicotine e-liquid concentrations

Recent evidence suggests that e-cigarette users tend to change their puffing behaviors when using e-liquids with reduced nicotine concentrations by taking longer and more frequent puffs. Using puffing regimens modelled on puffing topography data from 19 experienced e-cigarette users who switched between 18 and 6 mg/mL e-liquids with and without power adjustments, differences in daily exposure to carbonyl compounds and estimated changes in cancer risk were assessed by production of aerosols generated using a smoking machine and analyzed using gas and liquid chromatography. Significant differences across conditions were found for formaldehyde and acetaldehyde (p<0.01). Switching from a higher to a lower nicotine concentration was associated with greater exposure regardless of whether power settings were fixed or adjustable which is likely due to increased liquid consumption under lower nicotine concentration settings. Daily exposure for formaldehyde and acetaldehyde was higher for 17/19 participants when using low (6mg/mL) compared with high (18mg/mL) nicotine e-liquid concentration when power was fixed. When power adjustments were permitted, formaldehyde and acetaldehyde levels were higher respectively for 16/19 and 14/19 participants with the use of 6 compared with 18 mg/mL nicotine e-liquid

Modelling the species jump: towards assessing the risk of human infection from novel avian influenzas

The scientific understanding of the driving factors behind zoonotic and pandemic influenzas is hampered by complex interactions between viruses, animal hosts and humans. This complexity makes identifying influenza viruses of high zoonotic or pandemic risk, before they emerge from animal populations, extremely difficult and uncertain. As a first step towards assessing zoonotic risk of Influenza, we demonstrate a risk assessment framework to assess the relative likelihood of influenza A viruses, circulating in animal populations, making the species jump into humans. The intention is that such a risk assessment framework could assist decisionmakers to compare multiple influenza viruses for zoonotic potential and hence to develop appropriate strain-specific control measures. It also provides a first step towards showing proof of principle for an eventual pandemic risk model. We show that the spatial and temporal epidemiology is as important in assessing the risk of an influenza A species jump as understanding the innate molecular capability of the virus.We also demonstrate data deficiencies that need to be addressed in order to consistently combine both epidemiological and molecular virology data into a risk assessment framework

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57&nbsp;keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9})  eV^{2}. From this, we derive an upper limit of 1.1&nbsp;eV (90%&nbsp;confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation

Neutral tritium gas reduction in the KATRIN differential pumping sections

The KArlsruhe TRItium Neutrino experiment (KATRIN) aims to measure the effective electron anti-neutrino mass with an unprecedented sensitivity of $0.2\,\mathrm{eV}/\mathrm{c}^2$, using $\beta$-electrons from tritium decay. The electrons are guided magnetically by a system of superconducting magnets through a vacuum beamline from the windowless gaseous tritium source through differential and cryogenic pumping sections to a high resolution spectrometer and a segmented silicon pin detector. At the same time tritium gas has to be prevented from entering the spectrometer. Therefore, the pumping sections have to reduce the tritium flow by more than 14 orders of magnitude. This paper describes the measurement of the reduction factor of the differential pumping section performed with high purity tritium gas during the first measurement campaigns of the KATRIN experiment. The reduction factor results are compared with previously performed simulations, as well as the stringent requirements of the KATRIN experiment.Comment: 19 pages, 4 figures, submitted to Vacuu

Commissioning of the vacuum system of the KATRIN Main Spectrometer

The KATRIN experiment will probe the neutrino mass by measuring the beta-electron energy spectrum near the endpoint of tritium beta-decay. An integral energy analysis will be performed by an electro-static spectrometer (Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a volume of 1240 m^3, and a complex inner electrode system with about 120000 individual parts. The strong magnetic field that guides the beta-electrons is provided by super-conducting solenoids at both ends of the spectrometer. Its influence on turbo-molecular pumps and vacuum gauges had to be considered. A system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter strips has been deployed and was tested during the commissioning of the spectrometer. In this paper the configuration, the commissioning with bake-out at 300{\deg}C, and the performance of this system are presented in detail. The vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is demonstrated that the performance of the system is already close to these stringent functional requirements for the KATRIN experiment, which will start at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure