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Electronic cigarette liquids (e-liquids) can contain a variety of chemicals to impart flavors, smells and pharmacological effects. Surveillance studies have identified hundreds of chemicals used in e-liquids that have known health and safety implications. Ethyl acetate has been identified as a common constituent of e-liquids. Ethyl acetate is rapidly hydrolyzed to ethanol in vivo. Animal studies have demonstrated that inhaling >2,000 mg/L ethyl acetate can lead to the accumulation of ethanol in the blood at concentrations >1,000 mg/L, or 0.10%. A "Heisenberg" e-liquid was submitted to the Laboratory for Forensic Toxicology Research for analysis after a random workplace drug test resulted in a breath test result of 0.019% for a safety-sensitive position employee. Analysis of this sample resulted in the detection of 1,488 ± 6 mg/L ethyl acetate. The evaluation of purchased "Heisenberg" e-liquids determined that these products contain ethyl acetate. The identification of ethyl acetate in e-liquids demonstrates poor regulatory oversight and enforcement that potentially has consequences for breath ethanol testing and interpretations. The accumulation of ethanol in the breath from the ingestion/inhalation of ethyl acetate from an e-liquid used prior to a breath test may contribute to the detection of ethanol. [ABSTRACT FROM AUTHOR]

Legal professionals and others have suggested that vaping electronic cigarettes (e-cigs) prior to or during ethanol breath testing may produce false positives. Preliminary breath tests (PBTs) and evidentiary breath tests (EBTs) measure ethanol in exhaled breath and standardized field sobriety tests (SFSTs) are used to assess impairment. Ethanol has been identified in e-cig liquids (e-liquids). Presented are a series of experiments designed to determine the mechanics of vaping ethanol using an e-cig and the effects of vaping ethanol on the SFSTs and breath tests used by law enforcement officers (LEO). Twelve participants (five females, age: 21–32 and seven males, age: 21–55), vaped either one or ten puffs of an e-liquid (0% or 20% ethanol). LEOs assessed impairment using SFSTs (12 and 42 min), PBTs (<1, 27, 32, 37 and 57 min) and EBTs (2, 29, 34, 39 and 59 min) post-vaping. A self-assessment test was administered post-vaping (22 and 52 min). Baseline responses for all measures were collected prior to vaping. Results demonstrated that ethanol in the e-liquids was aerosolized by e-cigs and produced particles that could reach the deep lung tissue based on mean-mass diameter. Ethanol was detected by PBT <3 min after participants vaped one (0.007–0.030 g/210 L) or ten puffs (013–0.074 g/210 L) of a 20% ethanol e-liquid. Ethanol was not detected by PBT at any subsequent time point. Ethanol was not detected by the EBT under any condition. Impairment was not indicated by the SFST. Some subjective effects were reported, but few statistically significant differences between conditions were indicated. A wait period prior to ethanol breath testing is not always mandated, depending on jurisdiction, or observed in all applications, such as workplace testing. The results demonstrate that a wait period must be employed to prevent vaping-related false-positive breath ethanol results. [ABSTRACT FROM AUTHOR]

Gamma-butyrolactone (GBL), a commonly used industrial solvent, is used recreationally as a central nervous system (CNS) depressant and, therefore, is a United States Drug Enforcement Agency List 1 chemical of the Controlled Substances Act. GBL was identified presumptively in the liquid from JUUL Virginia Tobacco flavored pods during routine untargeted screening analysis of e-cigarette products by gas chromatography–mass spectrometry (GC–MS). Methods for the analysis of GBL were developed for GC–MS and liquid chromatography–tandem mass spectrometry (LC–MS-MS) in the liquids and the aerosol generated from the liquid. Three flavors of JUUL pods available at the time of analysis were obtained by direct purchase from the manufacturer, purchase from a local vape shop and submission from a third party. The only liquid flavor to contain GBL was Virginia Tobacco, with an average of 0.37 mg/mL of GBL, and it was detected in the aerosol. Studies evaluating the pharmacological effects of inhaling GBL do not exist; however, a case report of chronic oral GBL ingestion indicates acute lung injury. The identification of GBL in an e-cigarette product purportedly compliant with federal regulation continues to demonstrate public health and public safety concerns. [ABSTRACT FROM AUTHOR]

Electronic cigarettes (e-cigarettes) have rapidly evolved since their introduction to the U.S. market. The rebuildable atomizer (RBA) offers user-driven modification to the heating element (coil) and wicking systems. Different coil materials can be chosen based on user needs and preferences. However, the heating element of an e-cigarette is believed to be one-source for toxic metal exposure. E-cigarette coils from Kanthal and nichrome wires were constructed in a contact and non-contact configuration and heated at four voltages. The maximum temperatures of the coils were measured by infrared temperature sensing when dry and when saturated with 100% vegetable glycerin or 100% propylene glycol. The metal composition of each coil was analyzed with Scanning Electron Microscopy-Energy-Dispersive X-Ray (SEM-EDX) when new, and subsequently after 1, 50, and 150 heat cycles when dry. The coils reached temperatures above 1000 °C when dry, but were below 300 °C in both liquid-saturated mediums. Metal analysis showed a decrease of 9–19% chromium and 39–58% iron in Kanthal wire and a decrease of 12–14% iron and 39–43% nickel in nichrome wire after 150 heat cycles. Significant metal loss was observed after one heat cycle for both coil alloys and configurations. The loss of metals from these heat cycles further suggests that the metals from the coils are potentially entering the aerosol of the e-cigarette, which can be inhaled by the user. [ABSTRACT FROM AUTHOR]

Rationale: Natural plant products have been used to promote health, prevent sickness, and treat various ailments. These products often consist of leaves, flowers, bark, roots, seeds, and/or other parts of the plant. Many of the pharmacologically active constituents of these products are known, but the pharmacology of these constituents may not be fully elucidated. Natural plant-based products are also available in various forms other than the raw plant material. A wide array of commercial products such as capsules, powders, extracts, and electronic cigarette (e-cigarette) electronic liquids (e-liquids) are readily available and can be purchased from various outlets, both store-based retailers and online. Newer e-cigarettes are often advertised as "heat not burn" and are used for "vaping" various forms of extracts including "waxes" and "dabs" and raw plant material. Methods: A single manufacturer was found online selling "24 different herbs" in powders, extracts, or e-liquids. These were advertised as "legal in the USA" and each product listed multiple effects. Eight e-liquids, six extracts (resins), and four powders from eight different "herbs," namely African dream, areca nut, blue lotus, damiana, kra thum na, kra thum kok, klip dagga, and wild lettuce, were purchased. An advertisement for these products stated, "Most people use the leaves, powder or resin in vaporizers." Direct analysis in real time AccuTOF™ mass spectrometry (DART-MS) was used to identify the psychoactive components in the natural products. Results: The psychoactive compounds that were identified in only two of the eight e-liquids, three of the five resins, and three of the four powders were arecaidine, arecoline, coumarin, entadamide, mitragynine, 7-hydroxymitragynine, and nuciferine. Conclusions: Psychoactive and potentially harmful substances were present in the powders and resins of the natural products. The newer types of e-cigarettes made for consuming natural products may increase their abuse potential. [ABSTRACT FROM AUTHOR]

The use of electronic cigarettes (e-cigs) has expanded from a nicotine delivery system to a general drug delivery system. The internet is rife with websites, blogs and forums informing users how to modify e-cigs to deliver illicit drugs while maintaining optimal drug delivery of their device. The goal of this study was to qualitatively identify the presence of methamphetamine in the aerosol produced by an e-cig and to quantitatively assess the effect voltage on the concentration of aerosolized methamphetamine. A KangerTech AeroTank electronic cigarette containing a 30, 60 or 120 mg/mL of methamphetamine in 50:50 propylene glycol: vegetable glycerin formulation was used to produce the aerosol. To qualitatively identify aerosolized methamphetamine, the aerosol was generated at 4.3 V, trapped in a simple glass trapping system, extracted using solid-phase microextraction (SPME), and analyzed by high-resolution Direct Analysis in Real Time AccuTOF™ Mass Spectrometry (DART-MS). To assess the effect of voltage on the concentration of aerosolized methamphetamine, the aerosol was generated at 3.9, 4.3 and 4.7 V, trapped and quantified using gas chromatography mass spectrometry (GC/MS). SPME-DART-MS and SPME-GC-MS demonstrated the aerosolization of methamphetamine. The concentration of aerosolized methamphetamine at 3.9, 4.3 and 4.7 V was not statistically different at 800 ± 600 ng/mL, 800 ± 600 ng/mL and 1,000 ± 800 ng/mL, respectively. The characterization of the vapors produced from e-liquids containing methamphetamine provides an understanding of the dose delivery dynamics of e-cigarettes. [ABSTRACT FROM AUTHOR]

Electronic cigarettes (e-cigs) deliver nicotine in an aerosol to the user that simulates the smoke of traditional cigarettes purportedly without the pathology of inhaling tobacco smoke due to the absence of combustion. Advanced versions of e-cigs enable the user to potentially moderate the concentration of drug in the aerosol by selecting from a range of voltages on the power supply. A method was developed to trap the aerosol produced by a KangerTech AeroTank, 1.8 Ω preassembled atomizer in order to analyze the concentration of nicotine and to evaluate the constituents of the aerosol at various voltages on the power supply. A 12-mg/mL formulation of nicotine in 50:50 propylene glycol (PG):vegetable glycerin (VG) was used to produce aerosol at 3.9, 4.3 and 4.7 V. The aerosol was trapped in a simple glass assemblage and analyzed by a 3200 Q Trap HPLC–MS-MS. The dose of nicotine delivered in the aerosol at 3.9, 4.3 and 4.7 V was determined to be 88 ± 12 μg, 91 ± 15 μg and 125 ± 22 μg. The average recovery of nicotine in the trap across the voltages was 99.8%. The glass trap system was an effective device for collecting the aerosol for analysis and an increase in drug yield was observed with increasing voltage from the power supply on the e-cig. The glass trap system was also used in combination with a 100-μm solid-phase microextraction fiber to capture the aerosol and analyze it via DART–MS and GC–MS. Four commercial e-liquids labeled to contain nicotine were aerosolized at 4.3 V. The pharmacologically active ingredient, nicotine, as well as PG, VG and a number of flavoring agents found in these formulations were identified. [ABSTRACT FROM AUTHOR]

Personal battery-powered vaporizers or electronic cigarettes were developed as an alternative to traditional cigarettes. The modern electronic cigarettes were patented in 2004 by Hon Lik in China. In May 2016, the US Food and Drug Administration (FDA) imposed regulatory statutes on e-cigarettes and their liquid formulations (e-liquids); prior to that, they were unregulated. E-liquids are typically composed of propylene glycol and/or glycerin, flavouring component(s), and active ingredient(s), such as nicotine. Fifty-six commercially available e-liquids, purchased from various sources, contained a variety of flavours and active ingredients. A headspace gas chromatography with flame ionization detector (HS-GC-FID) method was used to analyze these e-liquids for volatiles content. Only one of the e-liquids listed ethanol as a component. The chromatographic separation of volatiles was performed on a Restek BAC-1 column. A linear calibration was generated for ethanol with limits of detection and quantification (LOD/LOQ) of 0.05 mg/mL. Ethanol concentrations in the 56 e-liquids ranged from none detected to 206 mg/mL. The ethanol determined in these products may have been used in flavourants or a solvent; the reason for inclusion cannot be fully ascertained. The implications of vaporizing ethanol as an e-liquid component are unknown. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The blue lotus flower (Nymphea caerulea) is an Egyptian water lily containing apomorphine and nuciferine. Apomorphine has been described as a psychoactive alkaloid and is a non-selective dopamine agonist primarily used to treat Parkinson’s disease as it stimulates dopamine receptors and improves motor function. Nuciferine is an alkaloid associated with dopamine receptor blockade. Today, blue lotus flower is used as a sleep aid and anxiety reliever. The rebuildable dripping atomizer (RDA) is an electronic cigarette that allows direct application of an e-liquid onto the coil in the atomizer for aerosolization, compared to a typical electronic cigarette where the e-liquid is wicked from a storage vessel to the coil. Our laboratory received a dark-brown resin material from a concerned parent. The resin had been confiscated from an adolescent who had a reported history of marijuana use. The resin was later identified as blue lotus flower (N. caerulea). This resin, together with four commercially available blue lotus products, was analyzed for content. Apomorphine was detected in two samples, and nuciferine was detected in all five samples. The confiscated resin was determined to contain no apomorphine and 4300 ng/g of nuciferine. The nuciferine resin was shown to aerosolize using aRDA electric cigarette. [ABSTRACT FROM PUBLISHER]

Graphical abstract Highlights • Analysis of unregulated cannabidiol e-liquids potentially used for medical or health reasons. • Four CBD only e-liquids determined to contain 5F-ADB or dextromethorphan. • Illustrates the potential quality control issues that occur in an unregulated industry. Abstract Electronic cigarettes (e-cigarettes) were developed as an alternative method for nicotine delivery and had a significant surge in popularity. E-liquids are formulations used in e-cigarettes, and consist of a ratio of propylene glycol (PG) and vegetable glycerin (VG), a pharmaceutical and/or herbal remedy and, usually, a flavoring agent. Presented is the evaluation of nine cannabidiol (CBD) e-liquids from a single manufacturer for cannabinoids and other psychoactive compounds by Direct Analysis in Real Time Mass Spectrometry (DART-MS) and Gas Chromatography Mass Spectrometry (GC/MS). The analysis of these products resulted in the detection of CBD in all nine produces and the unexpected detections of 5-fluoro MDMB-PINACA (5F-ADB) in four of the products and dextromethorphan (DXM) in one of the products. The analysis of these products illustrates the potential quality control issues that can occur in an unregulated industry. CBD products are believed by many users to offer heath benefits, but the detection of a dangerous cannabimimetic, 5F-ADB, and DXM in these products illustrates the need for oversight. [ABSTRACT FROM AUTHOR]

Personal battery-powered vaporizers or electronic cigarettes were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. Electronic cigarettes and their e-cigarette liquid formulations are virtually unregulated. These formulations are typically composed of propylene glycol and/or glycerin, flavoring components and an active drug, such as nicotine. Twenty-seven e-cigarette liquid formulations that contain nicotine between 6 and 22 mg/L were acquired within the USA and analyzed by various methods to determine their contents. They were screened by Direct Analysis in Real Time™ Mass Spectrometry (DART-MS). Nicotinewas confirmed and quantitated by high-performance liquid chromatography- tandem mass spectrometry, and the glycol composition was confirmed and quantitated by gas chromatography-mass spectrometry. The DART-MS screening method was able to consistently identify the exact mass peaks resulting from the protonated molecular ion of nicotine, glycol and a number of flavor additives within 5 mmu. Nicotine concentrations were determined to range from 45 to 131% of the stated label concentration, with 18 of the 27 have >10% variance. Glycol composition was generally accurate to the product description, with only one exception where the propylene glycol to glycerin percentage ratio was stated as 50:50 and the determined concentration of propylene glycol to glycerin was 81:19 (% v/v). No unlabeled glycols were detected in these formulations. [ABSTRACT FROM AUTHOR]

Personal battery-powered vaporizers or electronic cigarettes were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke.With four states within the USA having legalized the cultivation, distribution and recreational use of marijuana and an additional 23 states plus the District of Columbia with laws that legalize marijuana in some form, it was inevitable that suppliers of legal marijuana would develop marijuana products for use in these electronic cigarettes. Presented is the analysis of one such marijuana electronic cigarette formulation sold under the brand name Liberty Reach. The cannabinoid concentrations in Liberty Reach as determined by high-performance liquid chromatography—triple quadrapole mass spectrometry (HPLC–MS-MS) were Δ9-tetrahydrocannabinol, 42.6% (w/v) and cannabidiol 0.5% (w/v). These concentrations were significantly lower than the labeled 69% Δ9-tetrahydrocannabinol and 1% cannabidiol. Furthermore, 4 cannabinoids, 13 marijuana terpenes, and propylene glycol were identified by a combination of Direct Analysis in Real Time-AccuTOF™ mass spectrometry (DART-MS), HPLC–MS-MS and gas chromatography–MS. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

MDMB-FUBINACA (aka MDMB(N)-Bz-F), chemical name Methyl (S)-2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate, a designer drug or a new psychoactive substance (NPS), was identified in three commercially available e-liquids formulated for electronic cigarette use. The e-liquids were evaluated using direct analysis in real time ion source attached to a time of flight mass spectrometer (DART-MS) and gas chromatograph mass spectrometer (GC-MS) to identify active ingredients/drugs, flavorants, and other possible constituents. The e-liquids were also evaluated for alcohol content by headspace gas chromatography with flame ionization detector (HS-GC-FID). The aerosol produced from the e-liquids by use of an e-cigarette was analyzed by solid phase micro-extraction gas chromatography mass spectrometry (SPME-GC-MS) to ensure delivery of the active ingredient/drug. Propylene glycol, vegetable glycerin, MDMB-FUBINACA, alcohol content and a flavor profile were determined for each of the e-liquids. MDMB-FUBINACA was determined to be the major active ingredient in all three e-liquids and was successfully detected by SPME-GC-MS in the aerosol generated by a KangerTech Aerotank clearomizer/electronic cigarette. [ABSTRACT FROM AUTHOR]