RESUMO
Biosolids are a byproduct of wastewater treatment that can be beneficially applied to agricultural land as a fertilizer. While U.S. regulations limit metals and pathogens in biosolids intended for land applications, no organic contaminants are currently regulated. Novel techniques can aid in detection, evaluation, and prioritization of biosolid-associated organic contaminants (BOCs). For example, nontargeted analysis (NTA) can detect a broad range of chemicals, producing data sets representing thousands of measured analytes that can be combined with computational toxicological tools to support human and ecological hazard assessment and prioritization. We combined NTA with a computer-based tool from the U.S. EPA, the Cheminformatics Hazard Comparison Module (HCM), to identify and prioritize BOCs present in U.S. and Canadian biosolids (n = 16). Four-hundred fifty-one features were detected in at least 80% of samples, with identities of 92 compounds confirmed or assigned probable structures. These compounds were primarily categorized as endogenous compounds, pharmaceuticals, industrial chemicals, and fragrances. Examples of top prioritized compounds were p-cresol and chlorophene, based on human health end points, and fludioxonil and triclocarban, based on ecological health end points. Combining NTA results with hazard comparison data allowed us to prioritize compounds to be included in future studies of the environmental fate and transport of BOCs.
Assuntos
Águas Residuárias , Águas Residuárias/química , Monitoramento Ambiental/métodos , Humanos , Compostos Orgânicos/análiseRESUMO
BACKGROUND: Urine is an abundant and useful medium for measuring biomarkers related to chemical exposures in infants and children. Identification of novel biomarkers is greatly enhanced with non-targeted analysis (NTA), a powerful methodology for broad chemical analysis of environmental and biological specimens. However, collecting urine in non-toilet trained children presents many challenges, and contamination from specimen collection can impact NTA results. OBJECTIVES: We optimized a caregiver-driven method for collecting urine from infants and children using cotton pads and commercially available disposable diapers for NTA and demonstrate its applicability to various children biomonitoring studies. METHODS: Experiments were first performed to evaluate the effects of processing method (i.e., centrifuge vs. syringe), storage temperature, and diaper brand on recovery of urine absorbed to cotton pads. Caregivers of 11 children (<2 years) used and retained diapers (with cotton pads) to collect their child's urine for 24 h. Specimens were analyzed via a NTA method implementing an exclusion list of ions related to contamination from collection materials. RESULTS: Centrifuging cotton pads through a small-pore membrane, compared to a manual syringe method, and storing diapers at 4 °C, compared to room temperature, resulted in larger volumes of recovered sample. This method was successfully implemented to recover urine from cotton pads collected in the field; between 5-9 diapers were collected per child in 24 h, and the total mean volume of urine recovered was 44.7 (range 26.7-71.1) mL. NTA yielded a list of compounds present in urine and/or stool that may hold promise as biomarkers of chemical exposures from a variety of sources. IMPACT STATEMENT: Infant and children urine is a valuable matrix for studies of the early life exposome, in that numerous biological markers of exposure and outcome can be derived from a single analysis. Depending on the nature of the exposure study, it may be the case that a simple collection method that can be facilitated by caregivers of young children is desirable, especially when time-integrated samples or large volumes of urine are needed. We describe the process for development and results of an optimized method for urine collection and analysis using commercially available diapers and non-target analysis.
Assuntos
Expossoma , Manejo de Espécimes , Humanos , Lactente , Pré-Escolar , Manejo de Espécimes/métodos , Biomarcadores , Monitoramento Biológico , FezesRESUMO
BACKGROUND: There are over 700,000 hairdressers in the United States, and it is estimated that >90% are female and 31% are Black or Hispanic/Latina. Racial and ethnic minorities in this workforce may be exposed to a unique mixture of potentially hazardous chemicals from products used and services provided. However, previous biomonitoring studies of hairdressers target a narrow list of compounds and few studies have investigated exposures among minority hairdressers. OBJECTIVE: To assess occupational chemical exposures in a sample of US-based Black and Latina hairdressers serving an ethnically diverse clientele by analyzing urine specimens with a suspect screening method. METHODS: Post-shift urine samples were collected from a sample of US female hairdressers (n = 23) and office workers (n = 17) and analyzed via reverse-phase liquid chromatography coupled to high-resolution mass spectrometry. Detected compounds were filtered based on peak area differences between groups and matching with a suspect screening list. When possible, compound identities were confirmed with reference standards. Possible exposure sources were evaluated for detected compounds. RESULTS: The developed workflow allowed for the detection of 24 compounds with median peak areas ≥2x greater among hairdressers compared to office workers. Product use categories (PUCs) and harmonized functional uses were searched for these compounds, including confirmed compounds methylparaben, ethylparaben, propylparaben, and 2-naphthol. Most product use categories were associated with "personal use" and included 11 different "hair styling and care" product types (e.g., hair conditioner, hair relaxer). Functional uses for compounds without associated PUCs included fragrance, hair and skin conditioning, hair dyeing, and UV stabilizer. SIGNIFICANCE: Our suspect screening approach detected several compounds not previously reported in biomonitoring studies of hairdressers. These results will help guide future studies to improve characterization of occupational chemical exposures in this workforce and inform exposure and risk mitigation strategies to reduce potential associated work-related health disparities.
Assuntos
Tinturas para Cabelo , Exposição Ocupacional , Humanos , Feminino , Masculino , Projetos Piloto , Exposição Ocupacional/análise , Tinturas para Cabelo/análise , Substâncias Perigosas , PeleRESUMO
The surge in electronic cigarette (e-cig) use in recent years has raised questions on chemical exposures that may result from vaping. Previous studies have focused on measuring known toxicants, particularly those present in traditional cigarettes, while fewer have investigated unknown compounds and transformation products formed during the vaping process in these diverse and constantly evolving products. The primary aim of this work was to apply liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and chemical fingerprinting techniques for the characterization of e-liquids and aerosols from a selection of popular e-cig products. We conducted nontarget and quantitative analyses of tobacco-flavored e-liquids and aerosols generated using four popular e-cig products: one disposable, two pod, and one tank/mod. Aerosols were collected using a condensation device and analyzed in solution alongside e-liquids by LC-HRMS. The number of compounds detected increased from e-liquids to aerosols in three of four commercial products, as did the proportion of condensed-hydrocarbon-like compounds, associated with combustion. Kendrick mass defect analysis suggested that some of the additional compounds detected in aerosols belonged to homologous series resulting from decomposition of high-molecular-weight compounds during vaping. Lipids in inhalable aerosols have been associated with severe respiratory effects, and lipid-like compounds were observed in aerosols as well as e-liquids analyzed. Six potentially hazardous additives and contaminants, including the industrial chemical tributylphosphine oxide and the stimulant caffeine, were identified and quantified in the e-cig liquids and aerosols analyzed. The obtained findings demonstrate the potential of nontarget LC-HRMS to identify previously unknown compounds and compound classes in e-cig liquids and aerosols, which is critical for the assessment of chemical exposures resulting from vaping.
Assuntos
Aerossóis/análise , Sistemas Eletrônicos de Liberação de Nicotina , Aromatizantes/análise , Cromatografia Líquida , Espectrometria de MassasRESUMO
Total urinary 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) concentrations are generally reported following cannabis administration. Few data are available for glucuronide and minor cannabinoid metabolite concentrations. All urine specimens from 11 frequent and 9 occasional cannabis users were analyzed for 11 cannabinoids for ~85 h by liquid chromatography with tandem mass spectrometry following controlled smoked, vaporized or oral 50.6 mg Δ9-tetrahydrocannabinol (THC) in a randomized, placebo-controlled, within-subject dosing design. No cannabidiol, cannabinol, cannabigerol, tetrahydrocannabivarin (THCV), THC, 11-OH-THC and Δ9-tetrahydrocannabinolic acid were detected in urine. Median THCCOOH-glucuronide maximum concentrations (Cmax) following smoked, vaporized and oral routes were 68.0, 26.7 and 360 µg/L for occasional and 378, 248 and 485 µg/L for frequent users, respectively. Median time to specific gravity-normalized Cmax (Tmax) was 5.1-7.9 h for all routes and all users. Median Cmax for THCCOOH, THC-glucuronide and 11-nor-9-carboxy-Δ9-THCV (THCVCOOH) were <7.5% of THCCOOH-glucuronide Cmax concentrations. Only THC-glucuronide mean Tmax differed between routes and groups, and was often present only in occasional users' first urine void. Multiple THCCOOH-glucuronide and THCCOOH peaks were observed. We also evaluated these urinary data with published models for determining recency of cannabis use. These urinary cannabinoid marker concentrations from occasional and frequent cannabis users following three routes of administration provide a scientific database to assess single urine concentrations in cannabis monitoring programs. New target analytes (CBD, CBN, CBG, THCV and phase II metabolites) were not found in urine. The results are important to officials in drug treatment, workplace and criminal justice drug monitoring programs, as well as policy makers with responsibility for cannabis regulations.
Assuntos
Canabinoides/urina , Glucuronídeos/urina , Detecção do Abuso de Substâncias/métodos , Administração Oral , Adulto , Canabidiol , Canabinol , Cannabis , Humanos , Fumar Maconha , FumaçaRESUMO
As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered. Active compounds contained 6.9 ± 0.95% (~50.6 mg) ∆9-tetrahydrocannabinol (THC). Repeated blood samples were obtained, and the following endocrine markers were measured: total ghrelin, acyl-ghrelin, leptin, glucagon-like peptide-1 (GLP-1), and insulin. Results showed a significant drug main effect (p = 0.001), as well as a significant drug × time-point interaction effect (p = 0.01) on insulin. The spike in blood insulin concentrations observed under the placebo condition (probably due to the intake of brownie) was blunted by cannabis administration. A significant drug main effect (p = 0.001), as well as a trend-level drug × time-point interaction effect (p = 0.08) was also detected for GLP-1, suggesting that GLP-1 concentrations were lower under cannabis, compared to the placebo condition. Finally, a significant drug main effect (p = 0.01) was found for total ghrelin, suggesting that total ghrelin concentrations during the oral cannabis session were higher than the smoked and vaporized cannabis sessions. In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism.
Assuntos
Cannabis , Apetite , Estudos Cross-Over , Método Duplo-Cego , Dronabinol , Grelina/análogos & derivados , Humanos , Laboratórios , FumaçaRESUMO
Variability in urine dilution complicates urine cannabinoid test interpretation. Normalizing urine cannabinoid concentrations to specific gravity (SG) or creatinine was proposed to account for donors' hydration states. In this study, all urine voids were individually collected from eight frequent and eight occasional cannabis users for up to 85 hours after each received on separate occasions 50.6 mg Δ9-tetrahydrocannabinol (THC) by smoking, vaporization, and oral ingestion in a randomized, within-subject, double-blind, double-dummy, placebo-controlled protocol. Each urine void was analyzed for 11 cannabinoids and phase I and II metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS), SG, and creatinine. Normalized urine concentrations were log10 transformed to create normal distributions, and Pearson correlation coefficients determined the degree of association between the two normalization methods. Repeated-measures linear regression determined if the degree of association differed by frequent or occasional cannabis use, or route of administration after adjusting for gender and time since dosing. Of 1880 urine samples examined, only 11-nor-9-carboxy-THC (THCCOOH), THCCOOH-glucuronide, THC-glucuronide, and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCVCOOH) were greater than the method's limits of quantification (LOQs). Associations between SG- and creatinine-normalized concentrations exceeded 0.90. Repeated-measures regression analysis found small but statistically significant differences in the degree of association between normalization methods for THCCOOH and THCCOOH-glucuronide in frequent vs occasional smokers, and in THCVCOOH and THC-glucuronide by route of administration. For the first time, SG- and creatinine-normalized urine cannabinoid concentrations were evaluated in frequent and occasional cannabis users and following oral, smoked, and inhaled cannabis. Both normalization methods reduced variability, improving the interpretation of urine cannabinoid concentrations and methods were strongly correlated.
Assuntos
Canabinoides/urina , Creatinina/urina , Fumar Maconha/urina , Administração Oral , Adulto , Método Duplo-Cego , Humanos , Pessoa de Meia-Idade , Efeito Placebo , Gravidade Específica , Volatilização , Adulto JovemRESUMO
BACKGROUND: Although smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. Few studies directly compare cannabis' subjective and physiological effects following multiple administration routes. METHODS: Subjective and physiological effects, and expired carbon monoxide (CO) were evaluated in frequent and occasional cannabis users following placebo (0.001% Δ9-tetrahydrocannabinol [THC]), smoked, vaporized, and oral cannabis (6.9% THC, â¼54mg). RESULTS: Participants' subjective ratings were significantly elevated compared to placebo after smoking and vaporization, while only occasional smokers' ratings were significantly elevated compared to placebo after oral dosing. Frequent smokers' maximum ratings were significantly different between inhaled and oral routes, while no differences in occasional smokers' maximum ratings between active routes were observed. Additionally, heart rate increases above baseline 0.5h after smoking (mean 12.2bpm) and vaporization (10.7bpm), and at 1.5h (13.0bpm) and 3h (10.2bpm) after oral dosing were significantly greater than changes after placebo, with no differences between frequent and occasional smokers. Finally, smoking produced significantly increased expired CO concentrations 0.25-6h post-dose compared to vaporization. CONCLUSIONS: All participants had significant elevations in subjective effects after smoking and vaporization, but only occasional smokers after oral cannabis, indicating partial tolerance to subjective effects with frequent exposure. There were no differences in occasional smokers' maximum subjective ratings across the three active administration routes. Vaporized cannabis is an attractive alternative for medicinal administrations over smoking or oral routes; effects occur quickly and doses can be titrated with minimal CO exposure. These results have strong implications for safety and abuse liability assessments.
Assuntos
Monóxido de Carbono/metabolismo , Fumar Maconha/metabolismo , Fumar Maconha/fisiopatologia , Fumar Maconha/psicologia , Processos Mentais/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Testes Respiratórios , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Adulto JovemRESUMO
BACKGROUND: Roadside oral fluid (OF) Δ9-tetrahydrocannabinol (THC) detection indicates recent cannabis intake. OF and blood THC pharmacokinetic data are limited and there are no on-site OF screening performance evaluations after controlled edible cannabis. CONTENT: We reviewed OF and blood cannabinoid pharmacokinetics and performance evaluations of the Draeger DrugTest®5000 (DT5000) and Alere™ DDS®2 (DDS2) on-site OF screening devices. We also present data from a controlled oral cannabis administration session. SUMMARY: OF THC maximum concentrations (Cmax) were similar in frequent as compared to occasional smokers, while blood THC Cmax were higher in frequent [mean (range) 17.7 (8.0-36.1) µg/L] smokers compared to occasional [8.2 (3.2-14.3) µg/L] smokers. Minor cannabinoids Δ9-tetrahydrocannabivarin and cannabigerol were never detected in blood, and not in OF by 5 or 8 h, respectively, with 0.3 µg/L cutoffs. Recommended performance (analytical sensitivity, specificity, and efficiency) criteria for screening devices of ≥80% are difficult to meet when maximizing true positive (TP) results with confirmation cutoffs below the screening cutoff. TPs were greatest with OF confirmation cutoffs of THC ≥1 and ≥2 µg/L, but analytical sensitivities were <80% due to false negative tests arising from confirmation cutoffs below the DT5000 and DDS2 screening cutoffs; all criteria were >80% with an OF THC ≥5 µg/L cutoff. Performance criteria also were >80% with a blood THC ≥5 µg/L confirmation cutoff; however, positive OF screening results might not confirm due to the time required to collect blood after a crash or police stop. OF confirmation is recommended for roadside OF screening.ClinicalTrials.gov identification number: NCT02177513.
Assuntos
Líquidos Corporais/metabolismo , Canabinoides/sangue , Canabinoides/farmacocinética , Dronabinol/análogos & derivados , Boca/metabolismo , Detecção do Abuso de Substâncias/métodos , Administração Oral , Adolescente , Adulto , Canabinoides/administração & dosagem , Dronabinol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Establishing science-based driving per se blood Δ9 -tetrahydrocannabinol (THC) limits is challenging, in part because of prolonged THC detection in chronic, frequent users. Therefore, documenting observable signs of impairment is important for driving under the influence of drugs. We evaluated frequent and occasional cannabis smokers' performance on the modified Romberg balance, one leg stand (OLS), and walk and turn (WAT) tasks, and pupil size effects following controlled placebo (0.001% THC), smoked, vaporized and oral (6.9% [~50.4 mg] THC) cannabis administration. Significant effects following inhaled doses were not observed due to delayed tasks administration 1.5 and 3.5 h post-dose, but significant impairment was observed after oral dosing (blood THC concentrations peaked 1.5-3.5 h post-dose). Occasional smokers' odds of exhibiting ≥2 clues on the OLS or WAT following oral dosing were 6.4 (95% CI 2.3-18.4) times higher than after placebo, with THC and 11-hydroxy-THC blood concentrations individually producing odds ratios of 1.3 (1.1-1.5) and 1.5 (1.3-1.8) for impairment in these tasks, respectively. Pupil sizes after oral dosing under the direct lighting condition were significantly larger than after placebo by mean (SE, 95% CI) 0.4 (0.1, 0.2-0.6) mm at 1.5 h and 0.5 (0.2, 0.2-0.8) mm at 3.5 h among all participants. Oral cannabis administration impaired occasional cannabis users' performance on the OLS and WAT tasks compared to placebo, supporting other reports showing these tasks are sensitive to cannabis-related impairment. Occasional smokers' impairment was related to blood THC and 11-hydroxy-THC concentrations. These are important public health policy findings as consumption of edible cannabis products increases. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
Assuntos
Atenção/efeitos dos fármacos , Cannabis/efeitos adversos , Fumar Maconha/efeitos adversos , Desempenho Psicomotor/efeitos dos fármacos , Pupila/efeitos dos fármacos , Detecção do Abuso de Substâncias/métodos , Administração Oral , Adolescente , Adulto , Método Duplo-Cego , Humanos , Exposição por Inalação , Fumar Maconha/psicologia , Pessoa de Meia-Idade , Análise e Desempenho de Tarefas , Volatilização , Caminhada , Adulto JovemRESUMO
Oral fluid (OF) is an important matrix for monitoring drugs. Smoking cannabis is common, but vaporization and edible consumption also are popular. OF pharmacokinetics are available for controlled smoked cannabis, but few data exist for vaporized and oral routes. Frequent and occasional cannabis smokers were recruited as participants for four dosing sessions including one active (6.9% Δ9 -tetrahydrocannabinol, THC) or placebo cannabis-containing brownie, followed by one active or placebo cigarette, or one active or placebo vaporized cannabis dose. Only one active dose was administered per session. OF was collected before and up to 54 (occasional) or 72 (frequent) h after dosing from cannabis smokers. THC, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabigerol (CBG) were quantified by liquid chromatography-tandem mass spectrometry. OF cannabinoid Cmax occurred during or immediately after cannabis consumption due to oral mucosa contamination. Significantly greater THC Cmax and significantly later THCV, CBD, and CBG tlast were observed after smoked and vaporized cannabis compared to oral cannabis in frequent smokers only. No significant differences in THC, 11-OH-THC, THCV, CBD, or CBG tmax between routes were observed for either group. For occasional smokers, more 11-OH-THC and THCCOOH-positive specimens were observed after oral dosing than after inhaled routes, increasing % positive cannabinoid results and widening metabolite detection windows after oral cannabis consumption. Utilizing 0.3 µg/L THCV and CBG cut-offs resulted in detection windows indicative of recent cannabis intake. OF pharmacokinetics after high potency CBD cannabis are not yet available precluding its use currently as a marker of recent use. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Assuntos
Canabinoides/análise , Fumar Maconha/metabolismo , Saliva/química , Administração Oral , Adulto , Canabinoides/metabolismo , Cannabis/química , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/metabolismo , Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem , Volatilização , Adulto JovemRESUMO
BACKGROUND: There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ9-tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. METHODS: We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. RESULTS: Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 µg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. CONCLUSIONS: Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513.
Assuntos
Canabinoides/administração & dosagem , Canabinoides/farmacocinética , Fumar Maconha/sangue , Administração Oral , Adulto , Canabinoides/sangue , Estudos Cross-Over , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Volatilização , Adulto JovemRESUMO
Identifying recent cannabis intake is confounded by prolonged cannabinoid excretion in chronic frequent cannabis users. We previously observed detection times ≤2.1h for cannabidiol (CBD) and cannabinol (CBN) and Δ(9)-tetrahydrocannabinol (THC)-glucuronide in whole blood after smoking, suggesting their applicability for identifying recent intake. However, whole blood collection may not occur for up to 4h during driving under the influence of drugs investigations, making a recent-use marker with a 6-8h detection window helpful for improving whole blood cannabinoid interpretation. Other minor cannabinoids cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and its metabolite 11-nor-9-carboxy-THCV (THCVCOOH) might also be useful. We developed and validated a sensitive and specific liquid chromatography-tandem mass spectrometry method for quantification of THC, its phase I and glucuronide phase II metabolites, and 5 five minor cannabinoids. Cannabinoids were extracted from 200µL whole blood via disposable pipette extraction, separated on a C18 column, and detected via electrospray ionization in negative mode with scheduled multiple reaction mass spectrometric monitoring. Linear ranges were 0.5-100µg/L for THC and 11-nor-9-carboxy-THC (THCCOOH); 0.5-50µg/L for 11-hydroxy-THC (11-OH-THC), CBD, CBN, and THC-glucuronide; 1-50µg/L for CBG, THCV, and THCVCOOH; and 5-500µg/L for THCCOOH-glucuronide. Inter-day accuracy and precision at low, mid and high quality control (QC) concentrations were 95.1-113% and 2.4-8.5%, respectively (n=25). Extraction recoveries and matrix effects at low and high QC concentrations were 54.0-84.4% and -25.8-30.6%, respectively. By simultaneously monitoring multiple cannabinoids and metabolites, identification of recent cannabis administration or discrimination between licit medicinal and illicit recreational cannabis use can be improved.
Assuntos
Canabinoides/sangue , Cromatografia Líquida/métodos , Fumar Maconha , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodos , Biomarcadores/sangue , Canabidiol/sangue , Canabinoides/isolamento & purificação , Dronabinol/análogos & derivados , Dronabinol/sangue , Glucuronídeos/sangue , HumanosRESUMO
Methamphetamine is included in drug testing programmes due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks® VapoInhaler™ administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices and plasma via a fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Additionally, OF were analyzed with an on-site screening device. Sixteen participants received 7 Vicks® VapoInhaler™ doses according to manufacturer's recommendations. Specimens were collected before and up to 32 h after the first dose. No d-methamphetamine or d-amphetamine was detected in any sample. All participants had measurable OF l-methamphetamine with median maximum concentrations 14.8 and 16.1 µg/L in Quantisal™ and Oral-Eze® devices, respectively, after a median of 5 doses. One participant had measurable OF l-amphetamine with maximum concentrations 3.7 and 5.5 µg/L after 6 doses with the Quantisal™ and Oral-Eze® devices, respectively. There were no positive DrugTest® 5000 results. In the cutoff range 20-50 µg/L methamphetamine with amphetamine ≥limit of detection, 3.1-10.1% of specimens were positive; first positive results were observed after 1-4 doses. Two participants had detectable plasma l-methamphetamine, with maximum observed concentrations 6.3 and 10.0 µg/L after 2 and 5 doses, respectively. Positive OF and plasma methamphetamine results are possible after Vicks® VapoInhaler™ administration. Chiral confirmatory analyses are necessary to rule out VapoInhaler™ intake. Implementing a selective d-methamphetamine screening assay can help eliminate false-positive OF results.
Assuntos
Anfetamina/análise , Anfetamina/sangue , Estimulantes do Sistema Nervoso Central/análise , Estimulantes do Sistema Nervoso Central/sangue , Metanfetamina/análise , Metanfetamina/sangue , Saliva/química , Administração Intranasal , Adulto , Anfetamina/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Cromatografia Líquida/métodos , Feminino , Humanos , Limite de Detecção , Masculino , Metanfetamina/administração & dosagem , Pessoa de Meia-Idade , Manejo de Espécimes/instrumentação , Estereoisomerismo , Detecção do Abuso de Substâncias/instrumentação , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodos , Adulto JovemRESUMO
Opiates are an important drug class in drug testing programmes. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only two addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45 g raw poppy seed doses, each containing 15.7 mg morphine and 3.1 mg codeine, 8 h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography-tandem mass spectrometry (1 µg/L morphine and codeine limits of quantification). Specimens (n = 459) were collected before and up to 32 h after the first dose. All specimens screened positive 0.5 h after dosing and remained positive for 0.5-13 h at Draeger 20 µg/L morphine cut-off. Maximum OF morphine and codeine concentrations (Cmax ) were 177 and 32.6 µg/L, with times to Cmax (Tmax ) of 0.5-1 h and 0.5-2.5 h post-dose, respectively. Windows of detection after the second dose extended at least 24 h for morphine and to 18 h for codeine. After both doses, the last morphine positive OF result was 1 h with 40 µg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cut-off, and 0.5 h with 95 µg/L cut-off, recently recommended by the Driving under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1 h after ingestion of 15.7 mg of morphine in raw poppy seeds, depending on the cut-off employed.
Assuntos
Codeína/análise , Morfina/análise , Papaver/química , Saliva/química , Sementes/química , Detecção do Abuso de Substâncias/métodos , Administração Oral , Adulto , Codeína/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/metabolismo , Saliva/metabolismo , Adulto JovemRESUMO
Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography-mass spectrometry (GC-MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC-MS method with >99% purity of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC-MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0-1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤ 4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT(®) II Plus, KIMS(®) II and DRI(®) had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT(®) II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation.
Assuntos
Anfetamina/urina , Metanfetamina/urina , Administração por Inalação , Adolescente , Adulto , Idoso , Creatinina/urina , Relação Dose-Resposta a Droga , Reações Falso-Positivas , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Voluntários Saudáveis , Humanos , Imunoensaio/métodos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Manejo de Espécimes , Estereoisomerismo , Detecção do Abuso de Substâncias/métodos , Adulto JovemRESUMO
Methamphetamine is a widely abused psychostimulant containing a chiral center. Consumption of over-the-counter and prescription medications may yield positive amphetamines results, but chiral separation of l- and d-methamphetamine and its metabolite amphetamine can help determine whether the source was licit or illicit. We present the first LC-MS/MS method with precolumn derivatization for methamphetamine and amphetamine chiral resolution in plasma and oral fluid collected with the Oral-Eze(®) and Quantisal™ devices. To 0.5mL plasma, 0.75mL Oral-Eze, or 1mL Quantisal specimen racemic d11-methamphetamine and amphetamine internal standards were added, followed by protein precipitation. Samples were centrifuged and supernatants loaded onto pre-conditioned Phenomenex(®) Strata™-XC Polymeric Strong Cation solid phase extraction columns. After washing, analytes were eluted with 5% ammonium hydroxide in methanol. The eluate was evaporated to dryness and reconstituted in water. Derivatization was performed with 1-fluoro-2,4-dinitrophenyl-5-l-alanineamide (Marfey's reagent) and heating at 45°C for 1h. Derivatized enantiomer separations were performed under isocratic conditions (methanol:water, 60:40) with a Phenomenex(®) Kinetex(®) 2.6µm C18 column. Analytes were identified and quantified by two MRM transitions and their ratio on a 3200 QTrap (AB Sciex) mass spectrometer in ESI negative mode. In all three matrices, the method was linear for all enantiomers from 1 to 500µg/L, with imprecision and accuracy of ≤11.3% and 85.3-108%, respectively. Extraction efficiencies ranged from 67.4 to 117% and matrix effects from -17.0 to 468%, with variation always ≤19.1%. Authentic plasma and OF specimens were collected from an IRB-approved study that included controlled Vicks(®) VapoInhaler™ administration. The present method is sensitive, selective, economic and rapid (separations accomplished in <10min), and improves methamphetamine result interpretation.
Assuntos
Alanina/análogos & derivados , Estimulantes do Sistema Nervoso Central/isolamento & purificação , Dinitrobenzenos/química , Metanfetamina/isolamento & purificação , Adulto , Alanina/química , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/química , Cromatografia Líquida de Alta Pressão/normas , Humanos , Limite de Detecção , Masculino , Metanfetamina/sangue , Metanfetamina/química , Padrões de Referência , Saliva/química , Espectrometria de Massas por Ionização por Electrospray/normas , Estereoisomerismo , Espectrometria de Massas em Tandem/normasRESUMO
Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45 g oral poppy seed doses 8 h apart, each containing 15.7 mg morphine and 3mg codeine. Urine was collected ad libitum up to 32 h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2000 and 300 µg/L cutoffs, and the ThermoFisher CEDIA(®) heroin metabolite (6-acetylmorphine, 6-AM) and Lin-Zhi 6-AM immunoassays with 10 µg/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32 h following dosing; 26.6% and 83.4% were positive for morphine at 2000 and 300 µg/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7522 µg/L with a median peak concentration of 5239 µg/L. The median first morphine-positive urine sample at 2000 µg/L cutoff concentration occurred at 6.6 h (1.2-12.1), with the last positive from 2.6 to 18 h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2000 µg/L, but 20.2% exceeded 300 µg/L, with peak concentrations of 658 µg/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300 µg/L cutoffs. The CEDIA 6-AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results.
Assuntos
Analgésicos Opioides/urina , Codeína/urina , Morfina/urina , Papaver , Sementes , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imunoensaio , MasculinoRESUMO
Oral fluid (OF) is an increasingly popular alternative matrix for drug testing, with cannabinoids being the most commonly identified illicit drug. Quantification of multiple OF cannabinoids and understanding differences in OF cannabinoid pharmacokinetics between frequent and occasional smokers improve test interpretation. The new Oral-Eze® OF collection device has an elution buffer that stabilizes analytes and improves drug recovery from the collection pad; however, its performance has not been independently evaluated. After controlled smoking of a 6.8% Δ(9) -tetrahydrocannabinol (THC) cannabis cigarette by frequent and occasional smokers, OF was collected with the Oral-Eze device for up to 30 h. Samples were analyzed for multiple cannabinoids by a validated 2D-GC-MS method. Frequent smokers had significantly greater OF THCCOOH concentrations than occasional smokers at all times, and showed positive results for a significantly longer time. We evaluated multiple cannabinoid cut-offs; the shortest last detection times were observed when THC ≥ 1 µg/L was combined with CBD or CBN ≥ 1 µg/L. With these cut-offs, last detection times(1-13.5 h) were not significantly different between groups, demonstrating suitability for short-term cannabinoid detection independent of smoking history. Cut-offs utilizing THC alone or combined with THCCOOH showed significantly different last detection times between groups. The widest detection windows were observed with THC ≥ 1 or 2 µg/L or THCCOOH ≥ 20 ng/L. Our data illustrate the effectiveness of the Oral-Eze® device for OF collection, the impact of self-administered smoked cannabis history on OF cannabinoid results, and the ability to improve interpretation and tailor OF cannabinoid cut-offs to fulfill the detection window needs of a given program.