Radioimmunoassay methods for the forensic analysis of cannabinoids in biological fluids
This thesis describes the synthesis of cannabinoid
derivatives leading to the eventual production of the
radiotracer ~8-THC-ll-oic acid-[125I]iodohistamide. This
compound has been used to develop a relatively simple
radioimmunoassay (RIA) for the detection of cannabinoid
metabolites in blood and urine. The assay shows good
sensitivity and broad specificity, detecting the major
~9-tetrahydrocannabinol (~9-THC) metabolites; ~9-THC-ll-oic
acid, its O-ester glucuronide and ll-hydroxy-~9_THC.
The combination of an improved high-performance liquid
chromatographic separation and the RIA gave a method
suitable for the separation, characterisation and
quantification of both parent cannabinoids and metabolites.
The combined technique is sensitive and reliable and suited
to routine forensic. analysis.
These methods have been used to study the
pharmacokinetics and metabolism of ~9-THC following oral
ingestion of cannabis resin. ~9-THC-ll-oic acid-O-ester
glucuronide was identified as a major plasma metabolite and
was shown to be the princip~\ urine metabolite detected wit}
the RIA. In contrast, unconjugated ~9-THC-ll-oic acid was
not excreted in the urine in significant amounts.
Metabolites could be detected in plasma for up to 5
days and in urine for up to 12 days after a moderate dose oj
~9-THC (20mg) in cannabis resin.
The plasma half-life for ~9-THC-ll-oic acid and its
glucuronide were determined as 22 ± 2hr and 21 ± 2hr
respectively (mean ± SEM, n = 4). The urine half-life for
total cannabinoid metabolites was found to be 25 ± lhr (mean
± SEM, n = 4).
Limited interpretation of plasma total metabolite/~9-
THC concentration ratios was shown to be possible, giving
an indication of time since ingestion.
A preliminary experiment has shown that passive
inhalation of cannabis smoke does not lead to detectable
concentrations of cannabinoid metabolites in plasma or