THC-COOH

Fig. 1 Concentrations reported for opiods and cannabinoids in surface water of different European countries. MOR morphine Nor-MOR nor-morphine 6ACM 6-monoacetyl morphine HER heroin MET methadone EDDP 2-ethylidene-l,5-dimethyl-3,3 diphenylpyrrolidine THC A9-tetrahydro-cannabinol THC-COOH 11-nor 9-carboxy-THC N/A Values not availabe, not measured...

Whilst for the analysis of plant material for cannabinoids both GC and HPLC are commonly used, in analytical procedures the employment of GC-based methods prevails for human forensic samples. Nonetheless, the usage of HPLC becomes more and more of interest in this field especially in combination with MS [115-120]. Besides the usage of deuterated samples as internal standards Fisher et al. [121] describe the use of a dibrominated THC-COOH (see 7.5). The usage of Thermospray-MS and electrochemical detection provide good performance and can replace the still-used conventional UV detector. Another advantage in the employment of HPLC rather than GC could be the integration of SPE cartridges, which are needed for sample preparation in the HPLC-system. 

Contrary to other studies, 6ACM and THC presented 100% removal in this study, but due to their low frequency of detection in raw wastewaters and then-absence in treated wastewaters (see Figs. 2 and 5). This fact also affects the overall satisfactory removal of opioids (88%) and cannabinoids (79%). However, removal of morphine, the opioid most frequently detected in wastewaters ranged between 46 and 100%, variability also observed by other authors. In the case of cannabinoids, removals reported are very diverse. The average poor removal observed for THC-COOH in the investigated WWTPs from the Ebro River basin (48%) results from occasionally higher concentrations of this analyte in treated wastewaters compared to raw wastewaters. This finding has also been reported in other studies [7, 19]. 

The consumption indicator is the metabolic byproduct excreted at the highest rate. It may be a metabolite, as it is the case for cocaine (BE) and heroin (MOR), or the drug itself, as it is the case of amphetamine-like compounds. THC, the most psychoactive cannabinoid of the cannabis herb, is highly metabolized before excretion, thus, the consumption indicator selected (THC-COOH) presents an excretion rate of 0.6%. Despite the fact that OH-THC presents a slightly higher excretion rate (2%), this analyte was not selected to back calculate cannabis use due... 

FIGURE 1.1 Structures of THC and THC-COOH, its main metabolite from urine. 

Recently, Quintela et al. [58] have determined THC and the carboxy metabolite in oral fluid using HPLC coupled to a quadrupole-TOF mass spectrometer. Extreme selectivity of detection and LLOQs of 0.1 and 0.5ng/mL, respectively, were achieved through accurate mass measurement. None of the real positive samples examined was found to contain THC-COOH. 

Marijuana may also be eaten (baked into cookies or brownies), brewed in tea, or swallowed in pill form. Much of oral THC is destroyed in the stomach, and more is destroyed via first-pass metabolism. THC is metabolized primarily in the liver to an active metabolite, 11-hydroxy-THC (11-OH-THC), that is further converted to the inactive carboxylated compound 11-nor-delta 9-THC-9-COOH (THC-COOH) and its glucuro-nide form. It is these metabolites that are tested for in urine samples. 

Metabolism is the major route of elimination of THC from the body as little is excreted unchanged. In humans, over 20 metabolites have been identified in urine and feces 26 Metabolism in humans involves allylic oxidation, epoxidation, aliphatic oxidation, decarboxylation, and conjugation. The two monohydroxy metabolites (Figure 4.7) 11-hydroxy (OH)-THC and 8-beta-hydroxy THC are active, with the former exhibiting similar activity and disposition to THC, while the latter is less potent. Plasma concentrations of 11-OH-THC are typically <10% of the THC concentration after marijuana smoking. Two additional hydroxy compounds have been identified, namely, 8-alpha-hydroxy-THC and 8,11-dihydroxy-THC, and are believed to be devoid of THC-like activity. Oxidation of 11-OH-THC produces the inactive metabolite, ll-nor-9-carboxy-THC, or THC-COOH. This metabolite may be conjugated with glucuronic acid and is excreted in substantial amounts in the urine. 

THC undergoes metabolic degradation in the liver, where it is hydroxylated to 11-hydroxy tetrahydrocannabinol (THC-llOH). The latter, still with psychoactive activity, is oxidized to A9-THC-COOH, an inactive metabolite which is conjugated as 1 l-nor-A9-tetrahydrocannabinol-9-carboxy-glucuronide (A9-THC-COOH-glu), more hydrophilic metabolite and therefore easily excreted in the urine [32],... 

Cannabis is extensively metabolized in the human to 11 hydroxy- and 8 3 hydroxy-A9-tetrahydrocannabinol (11 OH and SP OH-THC) and finally to 11 nor-A9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), which is conjugated with glucuronic acid to a variable extent. 

Only the detection in hair of metabolites would provide convincing evidence of cannabis abuse. The presence in hair of THC-COOH, which is not detected in cannabis smoke, can be considered as a potential marker of chronic cannabis exposure and evidence that THC excretion occurs in hair after active use. 

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