An evaluation of the cannabinoid content of the liquid and thermal degradation analysis of cannabis-labeled vape liquids.

Cannabidiol (CBD) vape pen usage has been on the rise given the changing political and scientific climate as well as the promotion of these delivery systems as a more accessible and lower-risk option for consumers. Despite being marketed as a safer way to use cannabis, CBD vape liquids are sold without restrictions or meticulous quality control procedures such as toxicological and clinical assessment, standards for product preservation, or investigative degradation analyses. Nine CBD-labeled vape liquid samples purchased and manufactured in the United States were evaluated and assessed for cannabinoid content. Quantification and validation of cannabinoids and matrix components was accomplished using gas and liquid chromatography with mass spectrometry analysis (GC-MS and LC-MS/MS) following liquid-liquid extraction with methanol. Samples degraded by temperature (analyzed by GC-MS) showed a greater disparity from the labeled CBD content compared with samples analyzed as purchased (by LC-MS/MS). Thermal degradation of the vape liquids showed increased levels of tetrahydrocannabinol (THC). Also, extended time and temperature degradation were evaluated in vape liquids by storing them for 15 months and then varying temperature conditions before analysis, which indicated CBD transformed into other cannabinoids leading to different cannabinoid content within the vape samples. Evaluation conducted on these vape liquids indicated the route of exposure, storage conditions, and length of storage could expose consumers to unintended cannabinoids and showed a concerning level of disagreement between the products' labeled cannabinoid content and the results generated by these analyses.

Quantification of Cannabis in Infused Consumer Products and Their Residues on Skin.

Cannabis consumer products are a $4.6 billion industry in the U.S. that is projected to exceed $14 billion by 2025. Despite an absence of U.S. Food and Drug Administration (FDA) regulation or clinical data, thousands of nutraceuticals, topical consumer products, and beauty products claim benefits of hemp or cannabidiol. However, a lack of required quality control measures prevents consumers from knowing the true concentration or purities of cannabis-labeled products. Thirteen over-the-counter consumer products were examined for the presence of cannabidiol (CBD), cannabinol (CBN), Δ9-tetrahydrocannabinol (THC), cannabidiolic acid (CBDA), and Δ9-tetrahydrocannabinolic acid A (THCA). Additionally, the efficacy of topical applications was investigated using a porcine skin model, in which particle size and zeta potential relate to skin permeability. Skin permeation was correlated to particle size and relative stability in skin-like conditions but not directly related to the CBD content, suggesting that topical products can be designed to enhance overall skin permeation. Of the products analyzed, all products have some traceable amount of cannabinoids, while seven products had multiple cannabinoids with quantifiable amounts. Overall, the need for further regulation is clear, as most products have apparent distinctions between their true and labeled contents.

Tell-Tale SNPs: The Role of CYP2B6 in Methadone Fatalities.

Cytochrome P450 (CYP) enzyme 2B6 plays a significant role in the stereo-selective metabolism of (S)-methadone to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine, an inactive methadone metabolite. Elevated (S)-methadone can cause cardiotoxicity by prolonging the QT interval of the heart's electrical cycle. Large inter-individual variability of methadone pharmacokinetics causes discordance in the relationship between dose, plasma concentrations and side effects. The purpose of this study was to determine if one or more single nucleotide polymorphisms (SNPs) located within the CYP2B6 gene contributes to a poor metabolizer phenotype for methadone in these fatal cases. The genetic analysis was conducted on 125 Caucasian methadone-only fatalities obtained from the West Virginia and Kentucky Offices of the Chief Medical Examiner. The frequency of eight exonic and intronic SNPs (rs2279344, rs3211371, rs3745274, rs4803419, rs8192709, rs8192719, rs12721655 and rs35979566) was determined. The frequencies of SNPs rs3745274 (*9, c516G > T, Q172H), and rs8192719 (21563 C > T) were enhanced in the methadone-only group. Higher blood methadone concentrations were observed in individuals who were genotyped homozygous for SNP rs3211371 (*5, c1459C > T, R487C). These results indicate that these three CYP2B6 SNPs are associated with methadone fatalities.

Fatal methadone toxicity: potential role of CYP3A4 genetic polymorphism.

Methadone is difficult to administer as a therapeutic agent because of a wide range of interindividual pharmacokinetics, likely due to genetic variability of the CYP450 enzymes responsible for metabolism to its principal metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). CYP3A4 is one of the primary CYP450 isoforms responsible for the metabolism of methadone to EDDP in humans. The purpose of this study was to evaluate the role of CYP3A4 genetic polymorphisms in accidental methadone fatalities. A study cohort consisting of 136 methadone-only and 92 combined methadone/benzodiazepine fatalities was selected from cases investigated at the West Virginia and Kentucky Offices of the Chief Medical Examiner. Seven single nucleotide polymorphisms (SNPs) were genotyped within the CYP3A4 gene. Observed allelic and genotypic frequencies were compared with expected frequencies obtained from The National Center for Biotechnology Information dbSNP database. SNPs rs2242480 and rs2740574 demonstrated an apparent enrichment within the methadone-only overdose fatalities compared with the control group and the general population. This enrichment was not apparent in the methadone/benzodiazepine cases for these two SNPs. Our findings indicate that there may be two or more SNPs on the CYP3A4 gene that cause or contribute to the methadone poor metabolizer phenotype.

Validation of blood and liver oxymorphone analysis using LC-MS-MS: concentrations in 30 fatal overdoses.

A sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitation of oxymorphone (OM) in human whole blood and liver. Sample preparation was done by solid-phase extraction, using deuterated OM as the internal standard. Separation was achieved using a Waters Aquity UPLC HSS T3 column. Analysis utilized positive electrospray ionization and multiple reaction monitoring. As part of the validation, studies were conducted to determine potential interference, selectivity, ion suppression/enhancement and carryover. Calibration model, limit of detection (LOD), lower limit of quantitation (LLOQ), precision and accuracy were also established. The linear range of the method was 2-500 ng/mL in blood and 5-500 ng/g in the liver. The LOD and LLOQ were 2 ng/mL for blood and 5 ng/g for the liver. Blood and/or liver specimens from 30 cases were analyzed. OM concentrations ranged from 23 to 554 ng/mL ( , n = 26) in blood and 48 to 1740 ng/g ( , n = 30) in the liver.