TY - JOUR
AU - Peace, Michelle, R
AB - Abstract 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. Introduction Originally known as electronic nicotine delivery systems, the modern electronic cigarette (e-cig) was invented in 2003 as an alternative to traditional tobacco cigarettes for the delivery of nicotine (1). This industry expanded rapidly from the original simple disposable e-cig to complex devices that allow for modifications, either to the electric liquid formulations (e-liquids) used and/or the device (1). By 2023, the estimated sales of all vaping products in the United States are projected to be $48 billion (2). A variety of electronic cigarettes are available on the market today. However, most e-cigarettes contain the same essential components: a battery, a cartridge or tank and atomizer (1, 3). The e-cigarette is powered by the battery that delivers a voltage to the atomizer, which then heats a coil. As the atomizer is heated, the e-liquid is rapidly heated on a coil, aerosolizes and quickly condenses into an aerosol cloud that is inhaled by the user. An e-liquid is typically composed of nicotine, flavoring agents and propylene glycol (PG), vegetable glycerin (VG), which have boiling temperature of 188°C and 290°C, respectively, and are effectively aerosolized at the coil temperatures of 145–344°C. (4, 5). At the onslaught of the e-cig revolution, no regulation was in place to monitor and manage the manufacturing, sale and distribution of e-cigarettes and e-liquids, facilitating their rapid expansion and product development (6–8). States such as New Hampshire, Maryland and Iowa began adopting legislations to try to control the sales to minors beginning in 2010 (9). In May 2016, the Food and Drug Administration passed the “Deeming Rule,” which defined e-cigarettes as tobacco products such that they could regulate the manufacture, import, packaging, labeling, advertising, promotion, sale and distribution of all e-cig devices in the same way as traditional cigarettes and smokeless tobacco (10). A significant reason to regulate these products was to ensure the safety and quality of e-cig products. E-liquid formulations have been found to vary significantly from labeled content around the world (11–15), and to contain drugs other than nicotine (DOTN). E-liquids with DOTN also vary from labeled content regularly, both in quantity of labeled drug in the e-liquid to complete absence of drug disclosure (16–21). Manufacturers of e-cigs have developed new devices to allow users to modify their “vaping” experience. Options for customization include modifying the atomizer coil type and configuration, varying the voltage of the e-cig, and formulating e-liquids with varying concentrations of nicotine or PG:VG ratio. The internet has a plethora of sources, including websites, blogs, forums and videos, that teach users how to modify e-liquid solutions and optimize their device in order to deliver illicit drugs such as methamphetamine (mAMP), tetrahydrocannabinol, heroin and synthetic cannabinoids (18, 20, 22, 23). Some e-cigarette models contain a well or cup to hold crystal, wax or plant material, instead of a tank and coil system for e-liquids, which is directly heated from the battery. These models are ostensibly for vaping DOTNs. Methamphetamine is a stimulant drug commonly smoked either out of a glass pipe or off a flat metal surface like foil; however, e-cigs offer a new method for inhaling the illicit drug. Methamphetamine is soluble in PG and VG, and with a boiling point of 212°C, can be easily aerosolized by an e-cigarette. Solid-phase microextraction (SPME) has been proven to be an effective technique to analyze volatile substances and has historically been used to characterize the smoke of traditional cigarettes. Recent studies have demonstrated SPME can characterize the aerosolized product of e-liquids. Direct Analysis in Real Time AccuTOF™ Mass Spectrometry (DART-MS) and gas chromatography mass spectrometry (GC-MS) have also been used in conjunction with SPME to screen and confirm drugs, respectively, in the aerosol generated by e-cigarettes (18, 19, 24, 25). This study employed SPME, DART-MS and GC-MS to analyze the aerosolized product of e-liquids formulated to contain mAMP. SPME and liquid–liquid extraction (LLE) were used to extract mAMP from aerosolized e-liquid. Qualitative analysis of the aerosolized product was conducted by DART-MS, GC-MS in order to identify the presence of mAMP in the aerosol. Quantitative analysis was conducted by GC-MS in order to assess the effect of voltage on the concentration of aerosolized mAMP. Pyrolysis products of mAMP generated by high temperatures in the e-cigarette were also evaluated. Materials and methods Reagent and supplies Methamphetamine hydrochloride was purchased from Sigma Aldrich (St Louis, MO). Methamphetamine and Methamphetamine-d11 were purchased from Cerilliant (Round Rock, TX). USP grade PG and VG were purchased from Wizard Labs (Orlando, FL). The e-cigarette model used in this study was a KangerTech Aerotank clearomizer (v2) attached to an eGo-V v2 variable voltage battery, purchased from 101vape.com (Carlsbad, CA) (Figure 1). A pre-assembled single coil was wrapped in non-contact configuration with 34-gauge Nichrome wire to 1.8 Ω, and a 2-mm diameter silica string was used as a wick (DiscountVapes.com, Orlando, FL). The components of the trapping system, glassware, tubing and fritted gas dispersion tube, were purchased from Colonial Scientific (Richmond, VA). The flow meter used with the trap system was purchased from Cole Parmer (Vernon Hills, IL). SPME fibers with 100 μm polydimethylsiloxane (PDMS) were purchased from Supelco (Bellefont, PA). HPLC-grade methanol was purchased from Pharmco-Aaper (Brookfield, CT) and used for all dilutions and preparations of stock and working solutions. Solvents used for the LLE included ammonium hydroxide and 1-chlorobutane. Ammonium hydroxide was purchased from Fisher Chemical (Pittsburgh, PA). 1-chlorobutane was purchased from Sigma Aldrich (St. Louis, MO). Polyethylene glycol (PEG) with an average molecular mass of 600 Da used for DART-MS calibration was acquired from ULTRA Inc. (North Kingstown, RI). Nitrogen and helium gases were obtained from Praxair and Airgas (Richmond, VA). Figure 1 Open in new tabDownload slide KangerTech AeroTank, 1.8 Ω preassembled atomizer with eGo-V2 variable voltage battery e-cigarette. Figure 1 Open in new tabDownload slide KangerTech AeroTank, 1.8 Ω preassembled atomizer with eGo-V2 variable voltage battery e-cigarette. Electronic liquids and trapping apparatus Three lab-formulated e-liquids were prepared in a 50:50 (v:v) mixture of PG and VG to contain three concentrations of mAMP: 30 mg/mL, 60 mg/mL and 120 mg/mL. Samples were collected using a validated method to trap e-cigarette aerosol (11), consisting of two Erlenmeyer flasks connected in tandem by rubber tubing and attached to a vacuum set to a flow rate of 2.3 L/min (Figure 2). Glass wool was used to separate the primary trap from a secondary trap ensuring that the aerosol was captured in the primary flask. Each flask was filled with 150 mL deionized water to capture the aerosolized e-liquids. The e-cigarette was vaped for 4 s at 4.3 V. Upon completion, the tubing, flask, dispersion tube and glass wool were rinsed with 100 mL of DI H2O into the primary trap. The trap also contains a port in the stopper of the first flask to enable the insertion of a SPME fiber for direct sampling of the aerosol in the headspace (19, 25). Figure 2 Open in new tabDownload slide Simple trap assembly for the collection of e-cigarette aerosol. Figure 2 Open in new tabDownload slide Simple trap assembly for the collection of e-cigarette aerosol. Analysis by SPME SPME was performed using a 100 μm PDMS fiber to collect and capture the aerosol. The lab-formulated e-liquids containing mAMP were mechanically vaped into the trapping system where they were exposed to the SPME fiber for 5 min, after which the fiber was retracted. The SPME fibers were analyzed using the Direct Analysis in Real Time AccuTOF™ mass spectrometry (SPME-DART-MS) and gas chromatography mass spectrometry (SPME-GC/MS). The collection and analysis were performed in triplicate samplings for each e-liquid formulation for SPME-DART-MS and by five replicate samplings for SPME-GC/MS to ensure reproducibility. Instrument parameters A JEOL JMS T100LC Accu-TOF™ DART-MS controlled by Mass Center software version 1.3.4 (JEOL Inc. Tokyo, Japan) was used to qualitatively analyze the composition of the aerosol and determine the presence of mAMP (25). The SPME fiber was directly exposed into the helium stream of the DART-MS, which was operated in positive-ion mode with a helium stream of 350°C and a flow rate was set to 2.0 L/min. The discharge electrode needle voltage was operated at 150 V and the grid electrode at 250 V. The ion guide peak voltage was set to 400 V, reflectron voltage was 900 V, orifice 2 was set to 5 V and the ring lens was set to 3 V with orifice 1 set to 20, 30, 60 and 90 V while operating in function switching mode, with a single data file created for the four voltages. The range of masses measured ranged from 40–1,100 Da. The data was analyzed with TSS Pro V.3 by the creation of averaged, background subtracted, centroided mass spectra that were calibrated using PEG 600. Presumptive identification of all analytes was made when the exact mass was detected within 5 mDA of its calculated monoisotopic mass (M + H)+ and confirmed using primary reference materials that were used to match the fragmentation pattern in function switching mode. An Agilent 6890 N Gas Chromatograph coupled to a 5973 Mass Selective Detector (Santa Clara, CA) (GC-MS) was used to confirm the presence of mAMP in the aerosol. The chromatographic separation was performed on a HP-5MS column 30 m × 0.25 mm id × 0.25 mm (Agilent, Santa Clara, CA). The GC-MS was operated in splitless mode and the carrier gas was helium at a linear velocity of 35 cm/s. The SPME fiber was directly inserted into the injection port with a 15-min desorption time. The inlet temperature was set to 275°C. Oven temperature was operated from 120°C–300°C at a rate of 10°C/min and held for 12 min for a total runtime of 30 min. The mass spectrometer detector (MSD) was operated in full scan mode and select ion monitoring (SIM) mode. In scan mode, the MSD scanned a range of 40–550 m/z. In SIM mode, the MSD was operated with 58, 64, 91, 96, 134 m/z as the selected ions. Analytes were identified by retention times and ion ratios of reference materials, as well as full scan mass spectral match to the NIST 11.0 Mass Spectral Library. Effect of voltage power variation The impact of the e-cigarette voltage power on the aerosolization of mAMP was assessed. The three lab-formulated mAMP e-liquids were mechanically aerosolized using the trapping method previously described at three voltages: 3.9 V, 4.3 V and 4.7 V (Figure 2). Five replicates were completed for each e-liquid concentration at each voltage resulting in 45 samples total. The weight of the e-cig tank was recorded before and after each aerosol generation, and the differences in weight were used to determine the expected concentration per puff. An aliquot of 1,000 μL of water from the primary trap was fortified with 500 ng/mL of methamphetamine-d11. This internal standard was added to the aliquot instead of directly to the e-liquid being aerosolized in order to account for potential aerosolization inefficiencies resulting from the e-cig design. The aliquots were extracted with 200 μL of ammonium hydroxide and 100 μL 1-chlorobutane. Samples were vortexed for 5 min and then centrifuged at 3,000 rpm for 5 min. The 1-chlorobutane layer was transferred to a GC vial for analysis. The quantitation of mAMP samples was performed using the previously described GC-MS, but operated in a split mode of 6:1, with 1 μL injection volume. The carrier gas was helium at a linear velocity of 35 cm/s. The GC had an oven temperature of 120°C–200°C at a rate of 10°C/min then ramped to 280°C at a rate of 30°C/min for a total run time of 10.67 min. The MSD was operated in SIM mode with 58, 64, 91, 96, 134 m/z as the selected ions. Quantification was performed using 58 and 64 m/z as the quantitative ions for mAMP and mAMP-d11, respectively. The qualitative ions for mAMP were 91 and 134 m/z and 96 m/z for mAMP-d11. A six-point calibration curve was constructed with mAMP concentrations of 100, 200, 500, 750, 1,000 and 2,000 ng/mL with 500 ng/mL of mAMP-d11 as internal standard. The calibration curve was matrix-matched and was extracted from water using the method previously described. A linear regression was generated using the peak area ratio counts of mAMP and internal standard versus the theoretical calibrator concentrations and r2 > 0.9979 ± 0.0021 for all curves. The limit of quantitation was administratively set to 100 ng/mL. Six sets of controls were prepared from standard reference material and were included with each analytical batch: LOD QC (100 ng/mL), low QC (150 ng/mL), mid QC (600 ng/mL), high QC (1,500 ng/mL), a blank and a double blank. Intra-day precision and bias were determined by the largest percent coefficient of variation (%CV) and by the largest percent difference of the five runs (n = 6). Percent recovery was evaluated by comparing extracted standards to neat standards (n = 6). Carryover was assessed by injecting the lowest quality control (150 ng/mL) following the injection of the high-quality control (1,500 ng/mL). Figure 3 Open in new tabDownload slide SPME-DART-MS spectra of 60 mg/mL methamphetamine e-liquid. Figure 3 Open in new tabDownload slide SPME-DART-MS spectra of 60 mg/mL methamphetamine e-liquid. Figure 4 Open in new tabDownload slide Comparison of 120 mg/mL methamphetamine e-liquid and methamphetamine standard spectra by SPME-GC-MS. Figure 4 Open in new tabDownload slide Comparison of 120 mg/mL methamphetamine e-liquid and methamphetamine standard spectra by SPME-GC-MS. Statistical analysis was performed using JMP Pro 12.2.0 to assess the relationship between the concentration of aerosolized mAMP and voltage. The central limit theorem was used to assess the sample sizes of the groups and the distribution (asymmetric or symmetric) to determine the normality of the sample. A sample is considered to be normal if the data is normally or symmetrically distributed and/or the sample size is greater than or equal to 30. If these assumptions were not met, the sample was not considered to be normal. In order to assess the normality, the sample size, histogram and QQ-plot of each group were evaluated. Based on these results, the assumptions of normality were not met and Kruskal–Wallis test with a 5% significance level was used. Results Methamphetamine was successfully detected in the aerosol produced by the KangerTech Aerotank e-cigarette using the simple trapping system. The monoisotopic masses of PG, VG and mAMP were successfully identified by SPME-DART-MS at m/z of 77.0630, 93.0564 and 150.1293, respectively, at 20 V. Methamphetamine was also identified by comparing the fragmentation patterns in the samples at 20, 30, 60 and 90 V to the fragmentation pattern of the primary reference material of mAMP (Figure 3). The monoisotopic mass of mAMP and VG were observed at the 30 V along with fragments of mAMP at 119.0891 m/z and 91.0591 m/z. Methamphetamine was further fragmented at 60 V to 119.0891 m/z and 91.05777 m/z and at 90 V to 91.059 m/z and 65.041 m/z. This fragmentation across the four voltages is characteristic of mAMP regardless of concentration. The identification of PG, VG and mAMP by SPME-GC-MS was confirmed by the NIST database for PG and VG and the ion ratios generated by a mAMP reference material (Figure 4). A 6-day validation was completed for confirmation of mAMP using LLE and GC-MS. The measured concentrations of the four QC controls were within the ±20% limit of the theoretical concentrations (Table I). Inter-day precision was determined to be between 4% and 10% and inter-day bias was determined to be 4% and 14% for all quality control samples. Intra-day precision was determined to be 1% and 14% with an intra-day bias between −9% and 18% for all quality control samples. No carryover contamination was demonstrated by the lack of bias in the lowest quality control (150 ng/mL), which was run following the highest quality control (1,500 ng/mL). Percent recovery was calculated to be greater than 100% with a range of 102–107%. Table I Averaged Measured Methamphetamine Concentration of Quality Controls ± StdDev LOD (100 ng/mL) LOW (150 ng/mL) MID (600 ng/mL) HIGH (1,500 ng/mL) Day 1 112 ± 13 141 ± 3 630 ± 5 1,694 ± 58 Day 2 97 ± 9 168 ± 7 711 ± 25 1,803 ± 3 Day 3 98 ± 1 146 ± 19 645 ± 28 1,718 ± 26 Day 4 108 ± 15 158 ± 2 698 ± 16 1,784 ± 30 Day 5 120 ± 6 158 ± 8 668 ± 20 1,752 ± 63 Day 6 118 ± 11 170 ± 4 696 ± 18 1,667 ± 54 Interday 104 ± 11 158 ± 16 665 ± 28 1,709 ± 64 LOD (100 ng/mL) LOW (150 ng/mL) MID (600 ng/mL) HIGH (1,500 ng/mL) Day 1 112 ± 13 141 ± 3 630 ± 5 1,694 ± 58 Day 2 97 ± 9 168 ± 7 711 ± 25 1,803 ± 3 Day 3 98 ± 1 146 ± 19 645 ± 28 1,718 ± 26 Day 4 108 ± 15 158 ± 2 698 ± 16 1,784 ± 30 Day 5 120 ± 6 158 ± 8 668 ± 20 1,752 ± 63 Day 6 118 ± 11 170 ± 4 696 ± 18 1,667 ± 54 Interday 104 ± 11 158 ± 16 665 ± 28 1,709 ± 64 Open in new tab Table I Averaged Measured Methamphetamine Concentration of Quality Controls ± StdDev LOD (100 ng/mL) LOW (150 ng/mL) MID (600 ng/mL) HIGH (1,500 ng/mL) Day 1 112 ± 13 141 ± 3 630 ± 5 1,694 ± 58 Day 2 97 ± 9 168 ± 7 711 ± 25 1,803 ± 3 Day 3 98 ± 1 146 ± 19 645 ± 28 1,718 ± 26 Day 4 108 ± 15 158 ± 2 698 ± 16 1,784 ± 30 Day 5 120 ± 6 158 ± 8 668 ± 20 1,752 ± 63 Day 6 118 ± 11 170 ± 4 696 ± 18 1,667 ± 54 Interday 104 ± 11 158 ± 16 665 ± 28 1,709 ± 64 LOD (100 ng/mL) LOW (150 ng/mL) MID (600 ng/mL) HIGH (1,500 ng/mL) Day 1 112 ± 13 141 ± 3 630 ± 5 1,694 ± 58 Day 2 97 ± 9 168 ± 7 711 ± 25 1,803 ± 3 Day 3 98 ± 1 146 ± 19 645 ± 28 1,718 ± 26 Day 4 108 ± 15 158 ± 2 698 ± 16 1,784 ± 30 Day 5 120 ± 6 158 ± 8 668 ± 20 1,752 ± 63 Day 6 118 ± 11 170 ± 4 696 ± 18 1,667 ± 54 Interday 104 ± 11 158 ± 16 665 ± 28 1,709 ± 64 Open in new tab The effect of e-cig voltage on the concentration of mAMP in the aerosol was assessed by trapping the aerosol and analyzing by GC-MS. Each e-liquid was vaped at the three voltages and the mean theoretical concentration was calculated for each sample set (Table II). The concentration of mAMP was determined to be 800 ± 500 ng/mL, 800 ± 600 ng/mL and 1,000 ± 800 ng/mL at 3.9, 4.3 and 4.7 V, respectively (Table 2). Statistical analysis performed in JMP Pro 12.2.0 (Cary, NC) assessed the significant difference between the concentrations of aerosolized mAMP at each voltage. The results of the Kruskal–Wallis test concluded that the median concentrations of mAMP at each voltage were not significantly different. Since the data between voltages demonstrated no statistical difference, the average concentrations of mAMP by e-liquid concentration for the three voltages were calculated to be 500 ± 200 ng/mL, 1,000 ± 600 ng/mL and 700 ± 500 ng/mL from 30, 60 and 90 mg/mL mAMP e-liquid formulation, respectively (Table III). Pyrolysis products of mAMP (amphetamine, dimethylamphetamine, phenylacetone, N-formyl-, N-acetyl-, N-propionyl- and N-cyanomethyl-methamphetamine) were not observed in this study. The results of the Kruskal–Wallis test concluded that the average concentrations of mAMP for each e-liquid concentration were not different. Table II Mean Expected and Actual Concentration of Aerosolized Methamphetamine by Voltage Voltage E-liquid mAMP (mg/mL) Expected concentration aerosol mAMP (ng/mL) ± SD Actual concentration aerosol mAMP (ng/mL) ± SD 3.9 V 30 1,000 ± 80 700 ± 70 60 2,000 ± 200 1,000 ± 600 120 3,000 ± 1,000 800 ± 800 Average 2,000 ± 1,000 800 ± 600 4.3 V 30 900 ± 300 300 ± 90 60 2,000 ± 1,000 1,000 ± 700 120 5,000 ± 1,000 900 ± 400 Average 3,000 ± 2,000 800 ± 600 4.7 V 30 1,000 ± 300 600 ± 400 60 3,000 ± 200 2,000 ± 700 120 4,000 ± 600 600 ± 400 Average 3,000 ± 1,000 1,000 ± 800 Voltage E-liquid mAMP (mg/mL) Expected concentration aerosol mAMP (ng/mL) ± SD Actual concentration aerosol mAMP (ng/mL) ± SD 3.9 V 30 1,000 ± 80 700 ± 70 60 2,000 ± 200 1,000 ± 600 120 3,000 ± 1,000 800 ± 800 Average 2,000 ± 1,000 800 ± 600 4.3 V 30 900 ± 300 300 ± 90 60 2,000 ± 1,000 1,000 ± 700 120 5,000 ± 1,000 900 ± 400 Average 3,000 ± 2,000 800 ± 600 4.7 V 30 1,000 ± 300 600 ± 400 60 3,000 ± 200 2,000 ± 700 120 4,000 ± 600 600 ± 400 Average 3,000 ± 1,000 1,000 ± 800 Open in new tab Table II Mean Expected and Actual Concentration of Aerosolized Methamphetamine by Voltage Voltage E-liquid mAMP (mg/mL) Expected concentration aerosol mAMP (ng/mL) ± SD Actual concentration aerosol mAMP (ng/mL) ± SD 3.9 V 30 1,000 ± 80 700 ± 70 60 2,000 ± 200 1,000 ± 600 120 3,000 ± 1,000 800 ± 800 Average 2,000 ± 1,000 800 ± 600 4.3 V 30 900 ± 300 300 ± 90 60 2,000 ± 1,000 1,000 ± 700 120 5,000 ± 1,000 900 ± 400 Average 3,000 ± 2,000 800 ± 600 4.7 V 30 1,000 ± 300 600 ± 400 60 3,000 ± 200 2,000 ± 700 120 4,000 ± 600 600 ± 400 Average 3,000 ± 1,000 1,000 ± 800 Voltage E-liquid mAMP (mg/mL) Expected concentration aerosol mAMP (ng/mL) ± SD Actual concentration aerosol mAMP (ng/mL) ± SD 3.9 V 30 1,000 ± 80 700 ± 70 60 2,000 ± 200 1,000 ± 600 120 3,000 ± 1,000 800 ± 800 Average 2,000 ± 1,000 800 ± 600 4.3 V 30 900 ± 300 300 ± 90 60 2,000 ± 1,000 1,000 ± 700 120 5,000 ± 1,000 900 ± 400 Average 3,000 ± 2,000 800 ± 600 4.7 V 30 1,000 ± 300 600 ± 400 60 3,000 ± 200 2,000 ± 700 120 4,000 ± 600 600 ± 400 Average 3,000 ± 1,000 1,000 ± 800 Open in new tab Table III Mean Expected and Actual Concentration of Aerosolized Methamphetamine by E-liquid Concentration E-liquid mAMP (mg/mL) Mean expected concentration (ng/mL) ± SD Mean actual concentration (ng/mL) ± SD 30 900 ± 200 500 ± 200 60 2,000 ± 400 1,000 ± 600 120 4,000 ± 1,000 700 ± 500 E-liquid mAMP (mg/mL) Mean expected concentration (ng/mL) ± SD Mean actual concentration (ng/mL) ± SD 30 900 ± 200 500 ± 200 60 2,000 ± 400 1,000 ± 600 120 4,000 ± 1,000 700 ± 500 Open in new tab Table III Mean Expected and Actual Concentration of Aerosolized Methamphetamine by E-liquid Concentration E-liquid mAMP (mg/mL) Mean expected concentration (ng/mL) ± SD Mean actual concentration (ng/mL) ± SD 30 900 ± 200 500 ± 200 60 2,000 ± 400 1,000 ± 600 120 4,000 ± 1,000 700 ± 500 E-liquid mAMP (mg/mL) Mean expected concentration (ng/mL) ± SD Mean actual concentration (ng/mL) ± SD 30 900 ± 200 500 ± 200 60 2,000 ± 400 1,000 ± 600 120 4,000 ± 1,000 700 ± 500 Open in new tab Discussion This study demonstrated the efficacy of aerosolizing mAMP using an e-cigarette, as has been promulgated on social media and internet forums. SPME-DART-MS and SPME-GC-MS were quick and efficient qualitative techniques for assessing the aerosolization of mAMP from an e-cig with the comparison of the monoisotopic masses [M + H]+, the fragmentation patterns at 20, 30, 60 and 90 V, and the evaluation of ion ratios with primary reference material. In the effort to characterize the aerosolization efficacy of mAMP, the GC-MS quantitation of extracted mAMP from trapped aerosol was effective. A general consensus among e-cigarette users is that dose of drug in the aerosol increases as voltage of the e-cigarette battery increases (22, 26, 27). Research reports only modest increases in drug dosage with increasing voltage that is not statistically significant with wide differences of dose between puffs. The increase in dose with increasing voltage is also not practically significant with highly variable user vaping behaviors (25). The observed mean concentrations of aerosolized mAMP for the three concentrations of e-liquids and three voltages were 800 ng/mL, 800 ng/mL and 1,000 ng/mL at 3.9, 4.3 and 4.7 V, respectively (Table 2). The concentration of aerosolized mAMP ranged from 100 ng/mL to 2,000 ng/mL, with averages of 500 ± 200 ng/mL, 1,000 ± 600 ng/mL and 700 ± 500 ng/mL from 30, 60 and 90 mg/mL mAMP e-liquid formulation, respectively. Statistical analyses resulted in no statistical difference of concentration of aerosolized mAMP between voltages. The aerosol concentration was also statistically the same despite the increasing e-liquid concentrations of mAMP, indicating, again, that the devices are inconsistent drug delivery devices. Even so, the high standard deviations of the expected mean concentrations of mAMP in each puff, based on the difference in tank weight, demonstrated that the e-cig itself does not effectively aerosolize the same volume of e-liquid every time the coil is heated. Literature defines an average dose of smoked mAMP as 10–20 mg (28). The three concentrations of mAMP e-liquids (30, 60, 120 mg/mL) assessed in this study were selected to evaluate a conservative dosing. While puff topography varies significantly between e-cigarette users who are vaping nicotine, especially between experienced and novice users, average puff volume of an experienced user has been measured, on average, as 100 to 131 mL of aerosol for the first puff with 3.3–4 s puff duration, with a single session aerosol volume as approximately 1,500 mL (29, 30). These studies did not measure the concentration of drug in a puff or measure the volume change of e-liquid in the tank to define dose in terms of amount of product consumed. However, differences in measurements of puff topography indicate that users moderate their puff topography depending on their preferences and needs. In this study, the amount of e-liquid product consumed in a puff was 2 μL/puff, resulting in 0.24 mg/puff mAMP. While this is conceivably a low dose, vaping culture and behavior support long vaping sessions such that a user would still self-titrate drug exposure depending on the effects. Social media posts indicate that mAMP users are choosing e-cigarettes to vape mAMP in public spaces, especially since there is little to no suspicious odor associated with the aerosol and it is a socially acceptable tool (18, 19, 26). User philosophy is that the low dosing of mAMP from an e-cigarette in public can help to maintain a euphoric feeling and/or avoid withdrawal symptoms until they can achieve their next high with a higher dose in a private setting (26). Methamphetamine is an easily volatilized drug that has been well evaluated for pyrolysis products. Sato et al. demonstrated that as mAMP is heated, pyrolysis products are produced at temperatures greater than 315°C (31). Sekine et al. reported the major pyrolytic products of mAMP when analyzed by GC-MS include amphetamine, phenylacetone, dimethylamphetamine, N-formyl-, N-acetyl-, N-propionyl- and N-cyanomethyl-methamphetamine (32, 33). No pyrolysis products were observed in the aerosolization of mAMP from the e-cigarette. Reports of commercially available e-liquids containing marijuana extract, cannabidiol and novel psychoactive substances demonstrate the ability of e-cigarettes to aerosolize DOTN preparations of e-liquids. The presence of DOTNs, particularly illicit or recreational licit drugs, in a product is often indicated by unusually high price points for a product or by user reviews in social media and online drug forums. Reports of samples containing unadvertised contents of e-liquids including nuciferine, apomorphine, mitragynine, MDMB-FUBINACA, 5F-ADB, dextromethorphan, ethanol, cocaine, crack cocaine, heroin and LSD are emerging (17, 18, 20, 21, 34). The implication of these findings is that casual and/or uninformed users can unwittingly purchase a product that has been adulterated. Additionally, the inconsistent dosing of adulterants in e-liquids, in the e-liquid formulation and the aerosol, can lead to toxicological emergencies. Conclusion With the increasing popularity of these devices over the past several years, the use of these devices has expanded from its traditional use as a nicotine delivery system to a general drug delivery system for illicit and recreational licit psychoactive substances. The adulteration of e-liquids is a growing concern with a plethora of blogs, online forums and video tutorials that instruct users how to adulterate e-liquid solutions and manipulate their device to consume other drugs. Despite the growing public concern, information regarding the efficacy of these devices as an illicit drug delivery system is limited. 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TI - The Analysis of Aerosolized Methamphetamine From E-cigarettes Using High Resolution Mass Spectrometry and Gas Chromatography Mass Spectrometry
JO - Journal of Analytical Toxicology
DO - 10.1093/jat/bkz067
DA - 2019-09-10
UR - https://www.deepdyve.com/lp/oxford-university-press/the-analysis-of-aerosolized-methamphetamine-from-e-cigarettes-using-GEPPY5oO3v
SP - 592
VL - 43
IS - 8
DP - DeepDyve
ER -