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Additional file 1. Complete drug list.

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, flavoring component(s), and active ingredient(s), such as nicotine. Fifty-six commercially available e-liquids, purchased from various sources, contained a variety of flavors 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. A headspace gas chromatography with flame ionization detector HS-GC-FID method was used to analyze the e-liquids. 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 fifty-six e-liquids ranged from none detected to 206 mg/mL. The ethanol determined in these products may have been used in flavorants or a solvent; the reason for inclusion cannot be fully ascertained. The implications of vaporizing ethanol as an e-liquid component are unknown.

Since 24 states and the District of Columbia have legalized marijuana in some form, suppliers of legal marijuana have developed Cannabis sativa products for use in electronic cigarettes (e-cigarettes). Personal battery powered vaporizers, or e-cigarettes, were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. The liquid formulations used in these devices are comprised of an active ingredient such as nicotine mixed with vegetable glycerin (VG) and/or propylene glycol (PG) and flavorings. A significant active ingredient of C. sativa, cannabidiol (CBD), has been purported to have anti-convulsant, anti-nociceptive, and anti-psychotic properties. These properties have potential medical therapies such as intervention of addictive behaviors, treatments for epilepsy, management of pain for cancer patients, and treatments for schizophrenia. However, CBD extracted from C. sativa remains a DEA Schedule I drug since it has not been approved by the FDA for medical purposes. Two commercially available e-cigarette liquid formulations reported to contain 3.3 mg/mL of CBD as the active ingredient were evaluated. These products are not regulated by the FDA in manufacturing or in labeling of the products and were found to contain 6.5 and 7.6 mg/mL of CBD in VG and PG with a variety of flavoring agents. Presently, while labeled as to content, the quality control of manufacturers and the relative safety of these products is uncertain.

BACKGROUND: We evaluated a new EDDP [2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine] enzyme immunoassay (EDDPI; Lin‐Zhi International, Inc., Sunnyvale, CA) for the detection of this primary methadone urinary metabolite. METHODS: All specimens were tested with two different cutoff calibrators at 150 and 300 ng/ml EDDP on an ADVIA 1200 Chemistry System auto‐analyzer. Controls containing 0, −25% (negative control), and +25% (positive control) of the cutoff calibrators (Lin‐Zhi) were analyzed with each batch. All urine specimens were then analyzed by high‐pressure liquid chromatography/ mass spectrometry/mass spectrometry (HPLC‐MS/MS) for EDDP. RESULTS: Approximately, 42% (151) of the 362 specimens yielded positive results by the EDDP assay at 150 and/or 300 ng/ml cutoff values. Of these specimens, HPLC‐MS/MS confirmed the presence of EDDP > 25 ng/ml in all 151 specimens. No specimen yielding negative EDDPI results contained EDDP by HPLC/MS/MS. At 150 ng/ml cutoff, the EDDPI demonstrated a sensitivity of 1.00, a specificity of 0.986, and an overall agreement of HPLC/MS/MS of >99%. At 300 ng/ml cutoff, the EDDPI demonstrated a sensitivity of 1.00, a specificity of 0.959, and an overall agreement of HPLC/MS/MS results of 97.5%. CONCLUSION: The Lin‐Zhi EDDPI provides a precise, reliable method for the routine detection of methadone metabolite in urine specimens, particularly in pain management compliance testing.