A preliminary investigation on the distribution of cannabinoids in man

Gronewold, Antonia; Skopp, Gisela

doi:10.1016/j.forsciint.2011.04.010

Cited by 68 publications

(70 citation statements)

References 19 publications

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“…Recently, median plasma maximum concentrations were reported to be about 2.0 mg/l for CBD and 3.6 mg/l for CBN after smoking one 6.8% tetrahydrocannabinol cannabis cigarette (Schwope et al, 2011). However, plasma or whole-blood cannabinoid concentrations do not reflect tissue concentrations, particularly liver concentrations, which can be largely higher for CBD and CBN (Gronewold and Skopp, 2011). Consequently, the relevance of this cannabinoid/ethanol interaction on EtG formation remains uncertain and needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse

et al. 2012

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Ethyl glucuronide (EtG) determination is increasingly used in clinical and forensic toxicology to document ethanol consumption. The enzymes involved in EtG production, as well as potential interactions with common drugs of abuse, have not been extensively studied. Activities of human liver (HLM), kidney (HKM), and intestinal (HIM) microsomes, as well as of 12 major human recombinant UDP-glucuronosyltransferases (UGTs), toward ethanol (50 and 500 mM) were evaluated in vitro using liquid chromatography-tandem mass spectrometry. Enzyme kinetic parameters were determined for pooled microsomes and recombinant UGTs with significant activity. Individual contributions of UGTs were estimated using the relative activity factor approach, proposed for scaling activities obtained with cDNA-expressed enzymes to HLM. Interaction of morphine, codeine, lorazepam, oxazepam, nicotine, cotinine, cannabinol, and cannabidiol (5, 10, 15 mg/l) with ethanol (1.15, 4.6, 11.5 g/l; i.e., 25, 100, 250 mM) glucuronidation was assessed using pooled HLM. Ethanol glucuronidation intrinsic clearance (Cl int ) was 4 and 12.7 times higher for HLM than for HKM and HIM, respectively. All recombinant UGTs, except UGT1A1, 1A6, and 1A10, produced EtG in detectable amounts. UGT1A9 and 2B7 were the most active enzymes, each accounting for 17 and 33% of HLM Cl int , respectively. Only cannabinol and cannabidiol significantly affected ethanol glucuronidation. Cannabinol increased ethanol glucuronidation in a concentrationdependent manner, whereas cannabidiol significantly inhibited EtG formation in a noncompetitive manner (IC 50 = 1.17 mg/l; inhibition constant (K i ) = 3.1 mg/l). UGT1A9 and 2B7 are the main enzymes involved in ethanol glucuronidation. In addition, our results suggest that cannabinol and cannabidiol could significantly alter ethanol glucuronidation.

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Section: Discussionmentioning

confidence: 99%

Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse

et al. 2012

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“…The use of LC-MS/MS eliminates the need of costly and time-consuming alkaline and/ or enzymatic glucuronide hydrolysis, enabling direct measurement of free and glucuronidated THCCOOH. As native and isotopically labeled THCCOOH-glucuronide standards have become available only recently, few LC-MS/MS for quantifying THCCOOH-glucuronide in biological fluids exist [25,[29][30][31][32][33]. Schwope et al [25] and Gronewold et al [31] reported the only two existing methods for simultaneously measuring free and glucuronidated THCCOOH in whole blood, along with free and glucuronidated THC, 11-OH-THC, cannabinol and cannabidiol.…”

Section: Introductionmentioning

confidence: 99%

“…As native and isotopically labeled THCCOOH-glucuronide standards have become available only recently, few LC-MS/MS for quantifying THCCOOH-glucuronide in biological fluids exist [25,[29][30][31][32][33]. Schwope et al [25] and Gronewold et al [31] reported the only two existing methods for simultaneously measuring free and glucuronidated THCCOOH in whole blood, along with free and glucuronidated THC, 11-OH-THC, cannabinol and cannabidiol. Sample preparation consisted of protein precipitation followed by solid phase extraction [25] or liquid-liquid extraction [31] and chromatographic separation of the analytes was accomplished in 16 min and 10 min, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Schwope et al [25] and Gronewold et al [31] reported the only two existing methods for simultaneously measuring free and glucuronidated THCCOOH in whole blood, along with free and glucuronidated THC, 11-OH-THC, cannabinol and cannabidiol. Sample preparation consisted of protein precipitation followed by solid phase extraction [25] or liquid-liquid extraction [31] and chromatographic separation of the analytes was accomplished in 16 min and 10 min, respectively. In this work, a validated column-switching LC-MS/MS method for the direct and simultaneous quantification of THCCOOH and THCCOOH-glucuronide in whole blood is reported.…”

Section: Introductionmentioning

confidence: 99%

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Development of a rapid column-switching LC-MS/MS method for the quantification of THCCOOH and THCCOOH-glucuronide in whole blood for assessing cannabis consumption frequency

et al. 2016

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The concentration of 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol (THCCOOH) in whole blood is used as a parameter for assessing the consumption behavior of cannabis consumers. The blood level of THCCOOH-glucuronide might provide additional information about the frequency of cannabis use. To verify this assumption a column-switching liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the rapid and direct quantification of free and glucuronidated THCCOOH in human whole blood was newly developed. The method comprised protein precipitation, followed by injection of the processed sample onto a trapping column and subsequent gradient elution to an analytical column for separation and detection. The total LC run time was 4.5 min. Detection of the analytes was accomplished by electrospray ionization in positive ion mode and selected reaction monitoring using a triple stage quadrupole mass spectrometer. The method was fully validated by evaluating the following parameters: linearity, lower limit of quantification, accuracy and imprecision, selectivity, extraction efficiency, matrix effect, carry-over, dilution integrity, analyte stability and re-injection reproducibility. All acceptance criteria were analyzed and the predefined criteria met. Linearity ranged from 5.0 -500 µg/L for both analytes. The method was successfully applied to whole blood samples from a large collective of cannabis consumers, demonstrating its applicability in the forensic field.

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“…Les quelques études réalisées montrent systématiquement l'absence de THC dans l'HV [18,19]. Le THC-COOH a pu être mis en évidence dans l'HV sur quelques rares cas.…”

Section: Cannabinoïdes Dans L'humeur Vitréeunclassified

L’humeur vitrée en toxicologie médico-légale : revue de la littérature et applications

Brunet

Mura

2012

Ann Toxicol Anal

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A preliminary investigation on the distribution of cannabinoids in man

Cited by 68 publications

References 19 publications

Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse

Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse

Development of a rapid column-switching LC-MS/MS method for the quantification of THCCOOH and THCCOOH-glucuronide in whole blood for assessing cannabis consumption frequency

L’humeur vitrée en toxicologie médico-légale : revue de la littérature et applications

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