Simultaneous and Sensitive Analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in Plasma after Oral Application of Small Doses of THC and Cannabis Extract

Abstract

Besides the psychoactive Delta(9)-tetrahydrocannabinol (THC), hashish and marijuana as well as cannabis-based medicine extracts contain varying amounts of cannabidiol (CBD) and of the degradation product cannabinol (CBN). The additional determination of these compounds is interesting from forensic and medical points of view because it can be used for further proof of cannabis exposure and because CBD is known to modify the effects of THC. Therefore, a method for the simultaneous quantitative determination of THC, its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), CBD and CBN from plasma was developed. The method was based on automatic solid-phase extraction with C(18) ec columns, derivatization with N,O-bistrimethylsilyltrifluoroacetamide (BSTFA), and gas chromatography-electron impact ionization-mass spectrometry (GC-EI-MS) with deuterated standards. The limits of detection were between 0.15 and 0.29 ng/mL for THC, 11-OH-THC, THC-COOH, and CBD and 1.1 ng/mL for CBN. The method was applied in a prospective pharmacokinetic study after single oral administration of 10 mg THC alone or together with 5.4 mg CBD in cannabis extract. The maximum plasma concentrations after cannabis extract administration ranged between 1.2 and 10.3 ng/mL (mean 4.05 ng/mL) for THC, 1.8 and 12.3 ng/mL (mean 4.9 ng/mL) for 11-OH-THC, 19 and 71 ng/mL (mean 35 ng/mL) for THC-COOH, and 0.2 and 2.6 ng/mL (mean 0.95 ng/mg) for CBD. The peak concentrations (mean values) of THC, 11-OH-THC, THC-COOH, and CBD were observed at 56, 82, 115, and 60 min, respectively, after intake. CBN was not detected. Caused by the strong first-pass metabolism, the concentrations of the metabolites were increased during the first hours after drug administration when compared to literature data for smoking. Therefore, the concentration ratio 11-OH-THC/THC was discussed as a criterion for distinguishing oral from inhalative cannabis consumption.

Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol

“…An additional strength is inclusion of phase II THC-and THCCOOHglucuronides, as well as minor cannabinoids CBD and CBN. Limited blood and plasma controlledadministration data exist for these compounds (15)(16)(17)35 ). Metabolites provide valuable information on smoking history and time since last intake (34,36 ).…”

“…The few prior clinical studies had short (Յ6 h) time courses and limited metabolite analyses (10 -11 ). As medical cannabis use increases, data on plasma cannabinoids after vaporized cannabis are needed for therapeutic optimization, and blood cannabinoid data are needed for forensic DUI cannabis cases (17 ).…”

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

“…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).…”

“…With the added selectivity of tandem mass spectrometry, the LC-MS-MS methods have been able to use SPE with (34)(35)(36)(37) or without (33) prior protein precipitation. Only three of the methods mentioned above validated incorporation of CBD into the method (30,32,36). We have now developed and validated a GC-MS-MS method with a simple liquid-liquid extraction (LLE) procedure to analyze for THC, OH-THC, COOH-THC and CBD in plasma.…”

Potencial uso terapéutico de cannabis

“…En el plasma es posible detectar los metabolitos 11-O-THC y THC-COOH, los cuales aparecen en menor concentración que el THC en las primeras horas, pero pueden alcanzar niveles mayores y circular en el plasma más de 20 h después de dos dosis oral repetidas de THC. Respecto de lo anterior, se ha logrado mayor éxito en alcanzar concentraciones terapéuticamente efectivas usando la vía sublingual para el manejo del dolor neuropático y los síntomas de la esclerosis múltiple [47][48][49][50][51] .…”