Determination of Δ9-tetrahydrocannabinol, 11-nor-carboxy-Δ9-tetrahydrocannabinol and cannabidiol in human plasma and urine after a commercial cannabidiol oil product intake

Abstract

Purpose

Cannabidiol (CBD) products are widely used for pain relief, sleep improvement, management of seizures etc. Although the concentrations of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) in these products are low (≤0.3% w/w), it is important to investigate if its presence and/or that of its metabolite 11-nor-carboxy-Δ⁹-THC, is traceable in plasma and urine samples of individuals who take CBD oil products.

Methods

A sensitive GC/MS method for the determination of Δ⁹-THC, 11-nor-carboxy-Δ⁹-THC and CBD in plasma and urine samples was developed and validated. The sample preparation procedure included protein precipitation for plasma samples and hydrolysis for urine samples, solid-phase extraction and finally derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide) with 1% trimethylchlorosilane.

Results

For all analytes, the LOD and LOQ were 0.06 and 0.20 ng/mL, respectively. The calibration curves were linear (R² ≥ 0.992), and absolute recoveries were ≥91.7%. Accuracy and precision were within the accepted range. From the analysis of biologic samples of 10 human participants who were taking CBD oil, it was realized that Δ⁹-THC was not detected in urine, while 11-nor-carboxy-Δ⁹-THC (0.69–23.06 ng/mL) and CBD (0.29–96.78 ng/mL) were found in all urine samples. Regarding plasma samples, Δ⁹-THC (0.21–0.62 ng/mL) was detected in 10, 11-nor-carboxy-Δ⁹-THC (0.20–2.44 ng/mL) in 35, while CBD (0.20–1.58 ng/mL) in 25 out of 38 samples, respectively.

Conclusion

The results showed that Δ⁹-THC is likely to be found in plasma although at low concentrations. In addition, the detection of 11-nor-carboxy-Δ⁹-THC in both urine and plasma samples raises questions and concerns for the proper interpretation of toxicological results, especially considering Greece’s zero tolerance law applied in DUID and workplace cases.