Prevalence of ∆8-tetrahydrocannabinol carboxylic acid in workplace drug testing

Abstract

Abstract ∆8-Tetrahydrocannabinol (∆8-THC) recently became widely available as an alternative to cannabis. ∆8-THC is likely impairing and poses a threat to workplace and traffic safety. In the present study, the prevalence of ∆8-THC in workplace drug testing was investigated by analyzing 1,504 urine specimens with a positive immunoassay cannabinoid initial test using a liquid chromatography–tandem mass spectrometry (LC–MS-MS) method quantifying 15 cannabinoid analytes after hydrolysis. ∆8-tetrahydrocannabinol-9-carboxylic acid (∆8-THC-COOH) was detected in 378 urine specimens (15 ng/mL cutoff), compared to 1,144 specimens containing ∆9-THC-COOH. The data could be divided into three general groups. There were 964 (76%) ∆9-THC-COOH-dominant (<10% ∆8-THC-COOH) and 139 (11%) ∆8-THC-COOH-dominant (>90% ∆8-THC-COOH) specimens, with the remaining 164 (13%) specimens showing a mixture of both analytes (>90% ∆8-THC-COOH). Similar concentrations of ∆9-THC-COOH (median 187 ng/mL) and ∆8-THC-COOH (150 ng/mL) as the dominant species support the use of similar cutoffs and decision rules for both analytes. Apart from the carboxylic acid metabolites, 11-hydroxy-∆9-tetrahydrocannabinol (11-OH-∆9-THC, n = 1,282), ∆9-tetrahydrocannabivarin-9-carboxylic acid (∆9-THCV-COOH, n = 1,058), ∆9-THC (n = 746) and 7-hydroxy-cannabidiol (7-OH-CBD, n = 506) were the most prevalent analytes. Two specimens (0.13%) contained ≥140 ng/mL ∆9-THC without ∆9-THC-COOH, which could be due to genetic variability in the drug-metabolizing enzyme CYP2C9 or an adulterant targeting ∆9-THC-COOH. The cannabinoid immunoassay was repeated, and five specimens (0.33%) generated negative initial tests despite ∆9-THC-COOH concentrations of 54–1,000 ng/mL, potentially indicative of adulteration. The use of ∆8-THC is widespread in the US population, and all forensic laboratories should consider adding ∆8-THC and/or ∆8-THC-COOH to their scope of testing. Similar urinary concentrations were observed for both analytes, indicating that the decision rules used for ∆9-THC-COOH are also appropriate for ∆8-THC-COOH.