Fast and sensitive UHPLC-MS/MS analysis of cannabinoids and their acid precursors in pharmaceutical preparations of medical cannabis and their metabolites in conventional and non-conventional biological matrices of treated individual

Abstract Monitoring pharmacological active compounds in pharmaceutical preparations of medical cannabis and in conventional and non-conventional biological matrices of treated individuals use requires both a wide linear range and sensitive detection. We have developed and validated a fast and sensitive method using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) for analysis of Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors Δ-9-tetrahydrocannabinolic acid A (THCA-A) and cannabidiolic acid (CBDA) and some major metabolites of THC such as 11-nor-9-carboxy-THC (THC-COOH), 11-hydroxy-THC (11-OH-THC), Δ-9-THC-Glucuronide (THC-GLUC) and THC–COOH–Glucuronide (THC–COOH–GLUC) in conventional (whole blood and urine) and non-conventional (oral fluid and sweat) of individual treated with medical cannabis preparation. Specifically, THC, THCA-A, CBD and CBD-A were determined in cannabis decoction and oil prepared to treat individuals. The method used positive electrospray ionization (ESI) mode to reach the sensitivity needed to detect minimal amounts of analytes under investigations exposure with limits of quantification ranging from 0.2 to 0.5 ng per milliliter (ng/mL) or ng per patch in case of collected sweat. The validation results indicated this method was accurate (average inter/intra-day error,