Ultrasensitive measurement of delta-9-tetrahydrocannabinol with a high energy dynode detector and electron-capture negative chemical-ionization mass spectrometry.

Plasma concentrations of delta-9-tetrahydrocannabinol, the principal psychoactive cannabinoid in marijuana, decline to values substantially less than 1 microgram/L within a few hours after a subject has smoked a marijuana cigarette. Using a single-quadrupole gas chromatograph-mass spectrometer (GC/MS) operated in the negative chemical-ionization mode and retrofitted with a High Energy Dynode detector system, we measured delta-9-tetrahydrocannabinol and a primary metabolite, 11-nor-delta-9-tetrahydrocannabinol-9-COOH. Using a trifluoroacetic anhydride derivatization procedure and the High Energy Dynode detector system, we improved by 6.25-fold the limit of detection for delta-9-tetrahydrocannabinol in plasma over that obtained with the same GC/MS system without the new detector (80 vs 500 ng/L). The new detector system will thus permit further investigation of the post-distribution pharmacokinetics of delta-9-tetrahydrocannabinol and detection of delta-9-tetrahydrocannabinol in plasma for a longer time after ingestion of the drug in forensic cases. The High Energy Dynode detector system should be applicable to a wide variety of other GC/MS analyses that require significantly improved sensitivity.