Received on July 12, 2008
Accepted on December 16, 2008

Drug Monitoring and Toxicology

Intra- and Intersubject Whole Blood/Plasma Cannabinoid Ratios Determined by 2-Dimensional, Electron Impact GC-MS with Cryofocusing

¹ Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Biomedical Research Center, Baltimore, MD
² Washington State Patrol, Washington State Toxicology Laboratory, Seattle, WA
³ Molecular Neuropsychiatry, Intramural Research Program, National Institute on Drug Abuse, NIH, Biomedical Research Center, Baltimore, MD

^* To whom correspondence should be addressed. E-mail: mhuestis{at}intra.nida.nih.gov.

BACKGROUND: Whole-blood concentrations of ⁹-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) are approximately half of those in plasma due to high plasma protein binding and poor cannabinoid distribution into erythrocytes. Whole blood is frequently the only specimen available in forensic investigations; controlled cannabinoid administration studies provide scientific data for interpretation of cannabinoid tests but usually report plasma concentrations. Whole-blood/plasma cannabinoid ratios from simultaneously collected authentic specimens are rarely reported.

METHODS: We collected whole blood for 7 days from 32 individuals residing on a closed research unit. Part of the whole blood was processed to obtain plasma, and the whole blood and plasma were stored at -20 °C until analysis by validated 2-dimensional GC-MS methods.

RESULTS: We measured whole-blood/plasma cannabinoid ratios in 187 specimen pairs. Median (interquartile range) whole-blood/plasma ratios were 0.39 (0.28–0.48) for THC (n = 75), 0.56 (0.43–0.73) for 11-OH-THC (n = 17), and 0.37 (0.24–0.56) for THCCOOH (n = 187). Intrasubject variability was determined for the first time: 18.1%–56.6% CV (THC) and 10.8%–38.2% CV (THCCOOH). The mean whole-blood/plasma THC ratio was significantly lower than the THCCOOH ratio (P = 0.0001; 4 participants' mean THCCOOH ratios were >0.8).

CONCLUSIONS: Intra- and intersubject whole-blood/plasma THC and THCCOOH ratios will aid interpretation of whole-blood cannabinoid data.