Urinary excretion protiles of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and 11-hydroxy-Δ9-THC:: cannabinoid metabolites to creatinine ratio study IV

The objective of this study was to compare urinary excretion patterns of two cannabinoid metabolites in subjects with a history of chronic marijuana use. The first metabolite analyzed was nor-9-carboxy-Delta(9)-tetrahydrocannabinol (Delta(9)-THC-COOH), the major urinary cannabinoid metabolite that is pharmacologically inactive. The second metabolite 11-OH-Delta(9)-THC is an active cannabinoid metabolite and is not routinely measured. Urine specimens were collected from four subjects on 12-20 occasions greater than or equal to96 h apart in an uncontrolled clinical setting. Creatinine was analyzed in each urine specimen by the colorimetric modified Jaffe reaction on a SYVA 30R biochemical analyzer. All urine specimens analyzed for 11-OH-Delta(9)-THC had screened positive for cannabinoids with the EMIT II Plus cannabinoids assay (cut-off 50 ng/mL) on a SYVA 30R analyzer and submitted for Delta(9)-THC-COOH confirmation by GC-MS (cut-off concentration 15 ng/mL). Eleven-OH-Delta(9)-THC was measured by GC-MS with a cutoff concentration of 3 ng/mL. Both GC-MS methods for cannabinoid metabolites used deuterated internal standards for quantitative analysis. The mean (range) of urinary A9-THC-COOH concentration was 1153 ng/mL (78.7-2634) with a cut-off of 15 ng/mL. The mean (range) of Delta(9)-THC-COOH/creatinine ratios (ng/mL Delta(9)-THC-COOH/mmol/L creatinine) was 84.1 (8.1-122.1). The mean (range) urinary of 11-OH-Delta(9)-THC concentration was 387.6 ng/mL (11.9-783) with a cut-off of 3 ng/mL, and the mean (range) of 11-OH-Delta(9)-THC/creatinine ratio (ng/mL 11-OH-Delta(9)-THC/mmol/L creatinine) was 29.7 (1.2-40.7). Of the 63 urine specimens submitted for Delta(9)-THC-COOH confirmation by GC-MS, 59/63 urine specimens (94%) were positive for Delta(9)-THC-COOH and 51/63 (81%) were positive for 11-OH-Delta(9)-THC. Overall, the concentrations of 11-OH-Delta(9)-THC in urine specimens collected >96 h apart were lower than A9-THC-COOH concentrations in 50/51 of the urine specimens in this population. Further urinary cannabinoid excretion studies are needed to assess whether 11-OH-Delta(9)-THC analyses have a role when assessing previous marijuana or hashish use in chronic users whose urine specimens remain positive for Delta(9)-THC-COOH for an extended period of time after last drug use. (C) 2004 Elsevier Ireland Ltd. All rights reserved.