E-cigarette or vaping use-associated lung injury (EVALI) was identified with the incidents of a multi-state outbreak of acute lung injuries associated with the use of electronic cigarettes (e-cigs) and attributed to vitamin E acetate in off-market cannabis-based e-liquids. Aside from EVALI, hypersecretion of mucus, irritated nasal passages, and watery, red eyes have been defined as complaints associated with vaping standard nicotine-based e-liquids. The chemical composition of e-liquids varies between manufacturers and robust oversight of ingredients is lacking. Manufacturers use chemicals deemed “generally recognized as safe” (GRAS) by the FDA, a designation for chemicals used in foodstuffs to be ingested. Most “GRAS” chemicals are associated with at least one Global Harmonization System (GHS) warning class, ranging from irritant to toxic. Untargeted chemical analysis is critical to evaluate e-liquid products to determine chemical composition; equally important is the quantitation of components to help elucidate the potential harms from exceeding recommended exposure limits. Untargeted screening of e-liquids was accomplished using gas chromatography-mass spectrometry (GC-MS) and Direct Analysis in Real Time-AccuTOF™ mass spectrometry (DART-ToF-MS) and has identified 350 chemical constituents from 241 products analyzed. Nicotine, caffeine, menthol, and vitamin E were confirmed and quantitated by GC-MS, ethanol was confirmed and quantitated by headspace-gas chromatography-dual flame ionization detection (HS-GC-FID), and olivetol and cannabinoids were confirmed and quantitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Maximum identified concentrations of nicotine, caffeine, menthol, vitamin E, ethanol, olivetol, Δ9-tetrahydrocannabinol, and cannabidiol were 56.4, 26.9, 4.28, 307.9, 217.2, 399.6, 497.7, and 332.6 mg/ml, respectively. Evaluation of untargeted analysis and quantitation of unlabeled chemical components of e-liquids is essential to improving etiology of acute lung injury and less severe impacts of vaping, both short-term and long-term. The historical documentation of unlabeled ingredients can provide some insight for a retrospective analysis of health consequences and inform policy discussions.
Presented is the analysis of four cannabinoid-based products. These products were part of a case involving visual and auditory hallucinations that precipitated the commission of a felony and subsequent arrest. The products were labeled to contain Δ8-tetrahydrocannabinol (Δ8-THC) or THC acetate (THC-O-A). Primary reference materials were not available for Δ8-THC-O-A, Δ10-THC-O-A, cannabidiol di-acetate (CBD-di-O-A) or respective deuterated internal standards. THC-O-A and CBD-di-O-A standards were prepared by derivatizing Δ8-THC, Δ9-THC, Δ10-THC, CBD, Δ9-THC-d3 and CBD-d3 using acetic anhydride. The cannabinoid-based products were determined to contain Δ8-THC, Δ8-THC-O-A, Δ9-THC-O-A and CBD-di-O-A and/or other phytocannabinoids using three different analytical techniques. Direct analysis in real-time–time-of-flight mass spectrometry was used for identifying exact masses. A gas chromatograph–mass spectrometer was used for the identification of compounds and to quantitate THC-O-As in the products. A liquid chromatograph–tandem mass spectrometer was used to identify and quantitate phytocannabinoids and CBD-di-O-A in the products. To the authors’ knowledge, this is the first case report involving the identification of THC-O-As and CBD-di-O-A in commercially available products. Minimal clinical/pharmacological data is available for these emerging synthetic cannabinoids/novel psychoactive substances.
Gamma-Butyrolactone (GBL), a commonly used industrial solvent, is used recreationally as a central nervous system (CNS) depressant and, therefore, a United States Drug Enforcement Agency (DEA) 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 confirmation and quantitation 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 via submission from a 3rd 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.
A total of 222 clinical isolates were used to test the accuracy of Sensititre dried microtitration trays for determining minimum inhibitory concentrations (MICs) of antimicrobial agents. In comparison with an agar dilution technique, 89.5% of all the pairs of results were within one doubling dilution. The 2,420 pairs of MIC results with finite values gave a corresponding figure of 86.8%. Exclusion of sulfisoxazole results, which demonstrated a significant interlaboratory variation in accuracy, raised this value to 89.1%. Very good differentiation of /1-lactamaseproducing strains of Staphylococcus aureus (24 of 24 giving an MIC 2 0.25 ,ug/ ml) and Haemophilus influenzae (3 of 3 giving an MIC 2 32 pug/ml) was obtained with the Sensititre system. This method also clearly distinguished erythromycinresistant S. aureus strains (7 of 7 giving an MIC > 32 ,ug/ml) from the susceptible strains (26 of 28 giving an MIC ' 0.5 pg/ml plus 1 strain at 1.0 ,ug/ml and 1 at 2.0 pg/ml). Sensititre offers an accurate and convenient method of detenmining MICs comparable to those obtained with the agar dilution procedure, with the advantage of an extended shelf life when stored at room temperature.The Kirby-Bauer disk diffusion method is widely used for antimicrobial susceptibility tests, but there are limitations to this method, mainly because of the sensitivity of the test to changes in operator technique and also in the subsequent interpretation of zone diameters. In recent years there has been a move towards a more quantitative method, namely, the measurement of an antimicrobial agent's miniimum inhibitory concentration (MIC). To date this type of susceptibility testing has relied on freshly prepared dilutions of antimicrobial agents in nutrient media or on frozen microtitration trays, either made in the hospital's laboratory (9) or, more recently, brought in from an outside supplier (3). The frozen systems have to be stored at -20°C to retain the potencies of the antimicrobial drugs, and at this temperature the trays have a relatively limited storage life. A microtitration system, Sensititre, is now commercially available; it consists of plates containing dried antibiotic which are stable for 12 months at ambient temperature (data are on file with the manufacturer).A previous study has demonstrated the good perfornance of Sensititre when compared with another broth microdilution procedure, and also the high reproducibility of results obtained in several laboratories (6). This report compares Sensititre with the agar dilution procedure for MIC determinations. Particular emphasis was put on selecting organisms known to be resistant to antimicrobial agents. MATERIALS AND METHODSSensititre plates were supplied by Seward Laboratory, UAC House, Blackfriars Road, London
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