GC/MS and EMIT Analyses for Δ9-Tetrahydrocannabinol Metabolites in Plasma and Urine of Human Subjects*

McBurney, L J; Bobbie, B.; Sepp, L.A.

doi:10.1093/jat/10.2.56

Cited by 87 publications

(26 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10 mg of THC (GC/ MS detection limit 0.8 ng/ml) [93], and up to 13 d for deuterated THC in the blood of chronic cannabis users, who smoked four cigarettes containing deuterium-labeled THC (GC/MS detection limit 0.02 ng/ml) [109]. In the latter study, the terminal half-life of THC in plasma was determined to be ca.…”

Section: Smoked Cannabis-thcmentioning

confidence: 97%

See 1 more Smart Citation

Human Cannabinoid Pharmacokinetics

Huestis

2007

Chemistry & Biodiversity

899

775

View full text Add to dashboard Cite

Section: Smoked Cannabis-thcmentioning

confidence: 97%

“…Dihydroxylation of THC yields 8β,11-di-OH-THC. Excretion of 8β,11-di-OH-THC in urine was reported to be a good biomarker for recent cannabis use [93].…”

Section: Metabolismmentioning

confidence: 99%

Human Cannabinoid Pharmacokinetics

Huestis

2007

Chemistry & Biodiversity

899

775

View full text Add to dashboard Cite

“…Following marijuana smoking, peak plasma THC concentrations are achieved usually within 30 minutes (13)(14)(15). Plasma THC concentrations fall rapidly as the result of distribution into tissues and extensive metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…Gas chromatography-mass spectrometry (GC-MS) was initially used to measure THC and metabolites in human plasma (14,(25)(26)(27)(28)(29)(30). More recently 2-dimensional GC-MS has been employed to provide more sensitive analysis of plasma cannabinoids (31,32).…”

Section: Introductionmentioning

confidence: 99%

“…Because cannabinoid compounds are very lipophilic, extraction procedures are often complicated. Most early GC-MS method extraction procedures required a protein precipitation and/or ß-glucuronidase step was used purportedly to disrupt the binding of cannabinoid compounds to plasma proteins (14,25,26,29). Some utilized lengthy liquid-liquid procedures where either separate extracts were obtained for the neutral cannabinoid compounds (THC and OH-THC) and the acidic COOH-THC (25,26), or multiple extractions after derivatization (28).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography–Tandem Mass Spectrometry

et al. 2017

View full text Add to dashboard Cite

Two marijuana compounds of particular medical interest are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A gas chromatography-tandem mass spectrometry (GC-MS-MS) method was developed to test for CBD, THC, hydroxy-THC (OH-THC) and carboxy-THC (COOH-THC) in human plasma. Calibrators (THC and OH-THC, 0.1 to 100; CBD, 0.25 to 100; COOH-THC, 0.5-500 ng/mL) and controls (0.3, 5 and 80 ng/mL, except COOH-THC at 1.5, 25 and 400 ng/mL) were prepared in blank matrix. Deuterated (d 3 ) internal standards were added to 1-mL samples. Preparation involved acetonitrile precipitation, liquid-liquid extraction (hexane:ethyl acetate, 9:1), and MSTFA derivatization. An Agilent 7890 A GC was interfaced with an Agilent 7000 MS Triple Quadrupole. Selected reaction monitoring was employed. Blood samples were provided from a marijuana smoking study (two participants) and a CBD ingestion study (eight participants). Three analytes with the same transitions (THC, OH-THC and COOH-THC) were chromatographically separated. Matrix selectivity studies showed endogenous chromatographic peak area ratios (PAR) at the analyte retention times were <20% of the analyte limit of quantitation PAR. The intra-assay accuracy ranged from 83.5% to 118% of target and the intra-run imprecision ranged from 2.0% to 19.1%. The inter-assay accuracy ranged from 90.3% to 104% of target and the inter-run imprecision ranged from 6.5% to 12.0%. Stability was established for 25 hours at room temperature, 207 days at −20°C, after three freeze-thaw cycles and for 26 days for rederivatized processed samples. After smoking marijuana predictable concentrations of THC, OH-THC and COOH-THC were seen; low concentrations of CBD were detected at early time points. In moderate users who had not smoked for at least 9 hours before ingesting an 800 mg oral dose of CBD, the method was sensitive enough to follow residual concentrations of THC and OH-THC; sustained COOH-THC concentrations over 50 ng/mL validated its higher analytical range.

show abstract

Immunoassays in Forensic Toxicology

Moody¹

2000

Encyclopedia of Analytical Chemistry

View full text Add to dashboard Cite

Forensic toxicology encompasses the determination of the presence and concentration of drugs, other xenobiotics and their metabolites in physiological fluids and organs and the interpretation of these findings as they may impact on legal issues. These include medical examiner investigations, driving under the influence and other transportation accident investigations, workplace pre‐employment, random and for‐cause drug testing and judicial monitoring of arrestees and parolees. Similar techniques are employed in emergency room clinical toxicology and to monitor the efficacy of substance abuse treatment. The introduction of immunoassays into forensic toxicology in the early 1970s has had a major impact on the speed and efficiency that samples can be screened for the presence of certain drug classes. For the most part, forensic toxicologists use commercial immunoassays directed primarily towards abused drugs. Commercial immunoassays developed for therapeutic monitoring of other drugs, veterinary drugs and pesticides, as well as immunoassays developed in research laboratories for specialized studies, may find a role in the forensic toxicology laboratory for specialized cases. Most immunoassays used for forensic toxicology are competitive. An antigen structurally similar to the target compound is conjugated to a signalling molecule and competes with target drug in a sample for antibody binding. Immunoassays are also classified as homogeneous and heterogeneous. Homogeneous assays do not separate the original sample from the final detection sample. They must use a signal that changes when antibody is bound. Homogeneous immunoassays include enzyme immunoassay (EIA) (enzyme activity decreases when bound), fluorescent polarization immunoassay (FPIA) (emission in a polar field increases when bound) and kinetic interaction of microparticles in solution (KIMS) immunoassay (lattice formation inhibited when bound). Heterogenous immunoassays include radioimmunoassay (RIA) and enzyme‐linked immunosorbent assay (ELISA) where unbound radiolabeled antigen and enzyme conjugated antigen, respectively, are removed from the sample before measurement. In general, the homogeneous immunoassays are more ameniable to full automation, and thereby quicker throughput. The heterogeneous immunoassays are less susceptible to matrix interference, and thereby more versatile with nonurine matrices. While most commercial immunoassays have been developed for a urine matrix, they have been applied by forensic toxicologists to other matrices, including blood, hair, saliva, sweat, tissue homogenates, blood stains and most other physiological samples that may be of value in the investigation. The use of nonurine matrices must contend with two factors. With the exception of parenchymal tissues, the concentration of the target compound is often lower and the sensitivity of the immunoassay may be limiting. In addition, the nonurine matrix usually is much more complex in its composition. Sample pretreatments that range from simple deproteinations to multistep extractions to remove matrix components and/or concentrate the sample are often required. The heterogenous RIAs and ELISAs usually require less rigorous, if any, pretreatments. Interpretation of immunoassay results must take into consideration the limits of detection of the assay, the cross‐reactivity of the antibody(ies) and the potential for interference. Appropriate controls should be included to demonstrate adequate signal separation from blanks (drug‐free sample in the same matrix). The concentration of the low control is often determined by the sensitivity of the assay, or in workplace testing programs by administratively determined cutoffs that draw the line between a negative and presumptive positive. The ability of the antibody to detect compounds other than the target compound (its cross‐reactivity) can be a useful characteristic or, when the drugs that can be confirmed are limited, a nuisance. The amphetamines, barbiturates and benzodiazepines, in particular, all have a number of licit (and for amphetamines illicit) analogs that could be present in a sample. Cross‐reactivities are antibody‐source (i.e. manufacturer) dependent. Further testing to determine the immunoreactive compound often requires rigorous methodologies. In some instances, the potency of the drug and its poor cross‐reactivity make detection by immunoassay difficult (e.g. nitrosobenzodiazepines). Interference in immunoassays may arise from compounds that appear in the matrix during disease states, or those that are intentionally added to a sample in the hope of negating a positive test. These act through many different mechanisms and may decrease or increase the immunoassay test result. Immunoassays have added an extremely useful tool to the forensic toxicology investigation. They can be used to screen rapidly a large number of samples for the potential presence of a drug group. With rare exceptions (emergencies, limited sample volume), their use without a confirmation assay (e.g. gas or liquid chromatography/mass spectrometry (LC/MS)) is unwarranted, as it leads to a risk of improper test result interpretation.

show abstract

GC/MS and EMIT Analyses for Δ9-Tetrahydrocannabinol Metabolites in Plasma and Urine of Human Subjects*

Cited by 87 publications

References 32 publications

Human Cannabinoid Pharmacokinetics

Human Cannabinoid Pharmacokinetics

Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography–Tandem Mass Spectrometry

Immunoassays in Forensic Toxicology

Contact Info

Product

Resources

About