Simultaneous quantification of 18 different phytocannabinoids in serum using a highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method

The potential therapeutic effects of various phytocannabinoids and the availability of multiple cannabis-based medicines make it desirable to have an analytical method that simultaneously quantifies a wide range of cannabinoids in blood, beyond delta-9-tetrahydrocannabinol and its metabolites. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of 18 phytocannabinoids and cannabinoid metabolites in serum was developed and validated. The method enables simultaneous detection of delta-9tetrahydrocannabinol, cannabidiol, cannabinol, cannabigerol, cannabichromene, cannabicyclol, tetrahydrocannabivarin and cannabidivarin and their acidic precursors tetrahydocannabinolic acid A, cannabidiolic acid, cannabinolic acid, cannabigerolic acid, cannabichromenic acid, cannabicyclolic acid, tetrahydrocannabivarinic acid and cannabidivarinic acid as well as the delta-9-tetrahydrocannabinol metabolites 11-hydroxy-tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol. Limits of detection ranged from 0.0004 to 1 ng/mL and limits of quantification ranged from 0.004 to 2 ng/mL. Calibration curves of all analytes were linear over the whole calibration range. Recovery rates of 52 to 86% were obtained for all analytes except for cannabicyclol (49%), 11-nor-9-carboxy-tetrahydrocannabinol (46%), cannabichromenic acid (44%) and cannabidivarinic acid (36%). Acceptable bias and precision data were demonstrated for all analytes. The method was successfully applied to 55 forensic serum samples, obtained from the Institute of Legal Medicine Mainz.