Radioimmunoassay methods for the forensic analysis of cannabinoids in biological fluids

• Main Author: Law, Brian
• Published: University of Surrey 1983
• Subjects: 547; Organic chemistry
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.347771

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 urine.